PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 18038971-6 2007 Compared to FK506, the fragment-based FKBP12 inhibitors developed herein possess significant advantages as drug candidates. Tacrolimus 12-17 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 38-44 17082615-2 2006 Previous studies have shown that the immunosuppressants cyclosporin A or FK506, which interact with the peptidyl-propyl isomerases cyclophilin A and FK506-binding protein (FKBP12), respectively, block cytokine expression. Tacrolimus 73-78 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 172-178 17176100-2 2006 Inhibition of the protein phosphatase calcineurin (CaN), which has been implicated in the FK506-mediated blockade of T cell proliferation, was shown to involve a gain of function in the FKBP12/FK506 complex. Tacrolimus 193-198 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 186-192 17176100-5 2006 The different capacities of FK506/FKBP complexes to affect CaN activity are partially caused by substitutions corresponding to the amino acid side chains K34 and I90 of FKBP12. Tacrolimus 28-33 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 169-175 17176100-6 2006 Only the FK506 complexes of FKBP12, FKBP12.6, and FKBP51 showed high affinity to CaN; small interfering RNA against these FKBP allowed defining the contribution of individual FKBP in an NFAT reporter gene assay. Tacrolimus 9-14 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 28-34 16844742-1 2006 The absolute (standard) binding free energy of eight FK506-related ligands to FKBP12 is calculated using free energy perturbation molecular dynamics (FEP/MD) simulations with explicit solvent. Tacrolimus 53-58 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 78-84 16410343-3 2006 This effect was observed both with E. coli SlyD FKBP and with human FKBP12 and was counteracted by FK506, a specific inhibitor of FKBP. Tacrolimus 99-104 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 68-74 16490780-0 2006 Establishment of a cell model based on FKBP12 dimerization for screening of FK506-like neurotrophic small molecular compounds. Tacrolimus 76-81 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 39-45 16490780-7 2006 In this present study, the authors constructed a stable cell line, which underwent apoptosis upon treatment by AP20187, a wholly synthesized, cell-permeable dimeric FK506 derivative, based on FKBP12-mBax dimerization. Tacrolimus 165-170 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 192-198 16490780-8 2006 This AP20187-mediated apoptosis was rapidly reversed by the addition of an FKBP12-binding competitor molecule (FK506 or rapamycin), indicating that this cell line might be used to screen FK506 derivatives. Tacrolimus 111-116 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 75-81 16490780-8 2006 This AP20187-mediated apoptosis was rapidly reversed by the addition of an FKBP12-binding competitor molecule (FK506 or rapamycin), indicating that this cell line might be used to screen FK506 derivatives. Tacrolimus 187-192 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 75-81 15937899-10 2005 We predict that the E60A mutation will result in a significantly reduced affinity of FKBP12 for its ligand FK506. Tacrolimus 107-112 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 85-91 16290149-2 2006 The novel affinity resins bearing FK506 (6a, 6b) captured specific binding protein, FKBP12, with a small amount of nonspecific binding proteins. Tacrolimus 34-39 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 84-90 15144206-6 2004 We demonstrate that interactions of the type I receptor for TGFbeta with FKBP12 and the epidermal growth factor receptor (EGFR) with p85 are effectively disrupted by FK506 and EGFR kinase inhibitor AG1478, respectively. Tacrolimus 166-171 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 73-79 14623295-2 2003 The crystal structures of CN and its complexes with FKBP12-FK506 and cyclophilin-cyclosporin showed that the two structurally unrelated immunophilins-immunosuppressants bind to a common composite surface made up of the residues from both catalytic subunit and regulatory subunit of CN. Tacrolimus 59-64 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 52-58 14581219-4 2003 In comparing FKBP12-rapamycin complex and FKBP12-FK506 complex as well as FKBP12-GPI-1046 solution structure with these new complexes, significant volume and surface area effects and obvious contact changes were detected which are expected to cause their different binding energies-showing these two novel ligands will become more effective neuron regeneration drugs than GPI-1046, which is currently undergoing phase II clinical trail as a neurotrophic drug. Tacrolimus 49-54 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 42-48 14581219-4 2003 In comparing FKBP12-rapamycin complex and FKBP12-FK506 complex as well as FKBP12-GPI-1046 solution structure with these new complexes, significant volume and surface area effects and obvious contact changes were detected which are expected to cause their different binding energies-showing these two novel ligands will become more effective neuron regeneration drugs than GPI-1046, which is currently undergoing phase II clinical trail as a neurotrophic drug. Tacrolimus 49-54 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 42-48 14623295-4 2003 However, the binding pattern of FKBP12-FK506 such as hydrogen bonding is significantly different from that of CyPA-CsA. Tacrolimus 39-44 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 32-38 14599350-1 2002 FKBP12 is best known as the target of the widely used immunosuppressive drug FK506 but may also play a role in neuronal survival. Tacrolimus 77-82 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 12499534-7 2003 The Pro120 change corresponding to Gly89 in FKBP12 limits the conformational adaptation between the loop (residues 108-127) and FK506 and decreases the FK506 affinity, while the Lys121 substitution corresponding to Ile90 of FKBP12 destroys a key interaction between FKBP52-N and calcineurin. Tacrolimus 128-133 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 44-50 12499534-7 2003 The Pro120 change corresponding to Gly89 in FKBP12 limits the conformational adaptation between the loop (residues 108-127) and FK506 and decreases the FK506 affinity, while the Lys121 substitution corresponding to Ile90 of FKBP12 destroys a key interaction between FKBP52-N and calcineurin. Tacrolimus 152-157 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 44-50 12502928-1 2003 FKBP12 is a cytosolic FK506 binding protein that interacts with calcineurin and thereby mediates the immunosuppressive effects of FK506. Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 12137728-7 2002 Experimental evidence suggests that tacrolimus inhibits T-lymphocytes activation by binding to an intracellular protein, FKBP-12. Tacrolimus 36-46 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 121-128 12135494-7 2002 At low concentrations of FKBP12/FK506, CaN containing the alpha isoform is more sensitive to inhibition than CaN containing the beta isoform using the phosphopeptide substrates. Tacrolimus 32-37 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 25-31 11841938-1 2002 We used olefin metathesis to synthesize C40 derivatives of FK506 and measured their ability, when complexed to FKBP12, to inhibit calcineurin"s phosphatase activity. Tacrolimus 59-64 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 111-117 11673895-3 2001 The fusion protein was immobilized in avidin-coated multiwell plates, and varying concentrations of test ligands were allowed to compete with [3H]FK506 for FKBP12 sites on the plate. Tacrolimus 146-151 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 156-162 11054412-11 2001 12-kDa FK506-binding protein (FKBP12), however, could not be responsible for it, because FK506 treatment did not eliminate the suppression, in contrast to marked removal of 12-kDa FK506-binding protein from alpha-RyR. Tacrolimus 7-12 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 30-36 11557049-2 2001 FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. Tacrolimus 116-121 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 11557049-4 2001 Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12-glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. Tacrolimus 206-211 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 138-144 11418477-9 2001 Rapa exerts its apoptotic effect via a reversible binding to the cytosolic receptor protein FKBP-12, as demonstrated in competition experiments with FK506, which is structurally related to Rapa. Tacrolimus 149-154 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 92-99 10931176-2 2000 A singular FK506-like binding domain (FKBD) has about 12 kDa and occurs in the form of archetypal FKBP-12 and as a part of different proteins ranging in size from 13 to 135 kDa. Tacrolimus 11-16 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 98-105 10416209-2 1999 FK506 is complexed with an intracellular binding protein FKBP-12. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 57-64 10508685-6 1999 The approach has been established by isolating a full-length gene clone of FKBP12 (FK506-binding protein) from a human brain cDNA library using a biotinylated FK506 probe molecule. Tacrolimus 83-88 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 75-81 10465413-6 1999 While the crystal structure of the FK506-FKBP12-CN complex has been reported, no structure for a CsA-CyP CN complex has been determined. Tacrolimus 35-40 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 41-47 10465413-8 1999 The first stage of constructing this model consisted of using conformational comparison of CsA and FK506, GRID and GROUP analysis and restrained molecular dynamics to dock CsA into the FK506 binding site of the FK506-FKBP12-CN structure. Tacrolimus 99-104 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 217-223 10465413-8 1999 The first stage of constructing this model consisted of using conformational comparison of CsA and FK506, GRID and GROUP analysis and restrained molecular dynamics to dock CsA into the FK506 binding site of the FK506-FKBP12-CN structure. Tacrolimus 185-190 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 217-223 10465413-8 1999 The first stage of constructing this model consisted of using conformational comparison of CsA and FK506, GRID and GROUP analysis and restrained molecular dynamics to dock CsA into the FK506 binding site of the FK506-FKBP12-CN structure. Tacrolimus 185-190 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 217-223 9396011-9 1997 By influencing phosphorylation of neuronal nitric oxide synthase, FKBP12 regulates nitric oxide formation, which is reduced by FK506. Tacrolimus 127-132 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 66-72 9727000-4 1998 FK506.FKBP12 drug-immunophilin complexes inhibited the interaction of NFAT with activated calcineurin much more effectively than they inhibited the interaction with inactive calcineurin, suggesting that part of the interaction with activated calcineurin involved the enzyme active site. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 6-12 9697196-1 1998 Ligand-protein docking simulations are employed to analyze the binding energy landscape of the pipecolinyl fragment that serves as a recognition core of the FK506 ligand in binding with the FKBP12 protein. Tacrolimus 157-162 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 190-196 9697196-2 1998 This fragment acts as a molecular anchor that specifically binds within the protein active site in a unique binding mode, in harmony with the structure of the FK506-FKBP12 complex. Tacrolimus 159-164 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 165-171 9005438-1 1996 The 12 kDa FK506-binding protein FKBP12 is a cis-trans peptidyl-prolyl isomerase that binds the macrolides FK506 and rapamycin. Tacrolimus 11-16 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 33-39 9223178-0 1997 Mean field analysis of FKBP12 complexes with FK506 and rapamycin: implications for a role of crystallographic water molecules in molecular recognition and specificity. Tacrolimus 45-50 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 23-29 9223178-1 1997 Mean field analysis of FKBP12 complexes with FK506 and rapamycin has been performed by using structures obtained from molecular docking simulations on a simple, yet robust molecular recognition energy landscape. Tacrolimus 45-50 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 23-29 9223178-4 1997 The stability gap in the FKBP12-FK506 system is determined by two critical water molecules from the effector region that participate in a network of specific hydrogen bond interactions. Tacrolimus 32-37 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 25-31 9223178-5 1997 This interaction pattern protects the integrity and precision of the composite ligand-protein effector surface in the binary FKBP12-FK506 complex and is preserved in the crystal structure of the FKBP12-FK506-calcineurin ternary complex. Tacrolimus 132-137 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 125-131 9223178-5 1997 This interaction pattern protects the integrity and precision of the composite ligand-protein effector surface in the binary FKBP12-FK506 complex and is preserved in the crystal structure of the FKBP12-FK506-calcineurin ternary complex. Tacrolimus 132-137 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 195-201 9223178-5 1997 This interaction pattern protects the integrity and precision of the composite ligand-protein effector surface in the binary FKBP12-FK506 complex and is preserved in the crystal structure of the FKBP12-FK506-calcineurin ternary complex. Tacrolimus 202-207 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 125-131 9223178-5 1997 This interaction pattern protects the integrity and precision of the composite ligand-protein effector surface in the binary FKBP12-FK506 complex and is preserved in the crystal structure of the FKBP12-FK506-calcineurin ternary complex. Tacrolimus 202-207 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 195-201 9154824-7 1997 FK-506, another ligand of FKBP12 affecting the phosphatase calcineurin, did not antagonize but shared the effect of rapamycin. Tacrolimus 0-6 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 26-32 8955134-3 1996 FKBP59 and FKBP12 belong to the large family of immunophilins that bind the macrolide immunosuppressant drugs FK506 and rapamycin. Tacrolimus 110-115 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 11-17 8955134-10 1996 The formation of the complexes between FKBP59 or FKBP12 and FAP48 is prevented by FK506 and rapamycin in a dose-dependent manner. Tacrolimus 82-87 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 49-55 8994885-1 1996 Recently, two structures of the Ser/Thr phosphorylase calcineurin in complex with FK506 and its cognate immunophilin, FKBP12, have been reported, both solved by small pharmaceutical companies focused on structure-based drug design. Tacrolimus 82-87 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 118-124 8798476-2 1996 As the FK506 motif that competes with TbetaR-I for FKBP12 resembles an invariant Leu-Pro dipeptide in TbetaR-I, we replaced Leu193 and Pro194 with Ala, along with mutations across the Gly/Ser box. Tacrolimus 7-12 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 51-57 8702959-6 1996 FKBP12 dissociates from TbetaR-I in the presence of a high concentration of FK506. Tacrolimus 76-81 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 8880916-0 1996 Dynamic NMR studies of ligand-receptor interactions: design and analysis of a rapidly exchanging complex of FKBP-12/FK506 with a 24 kDa calcineurin fragment. Tacrolimus 116-121 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 108-115 8880916-2 1996 Using a combination of isotope labeling and isotope edited NMR, we have extended these techniques to characterize interactions of a much larger protein/drug complex, FKBP-12/ FK506 with its receptor protein, calcineurin. Tacrolimus 175-180 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 166-173 8880916-4 1996 Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Tacrolimus 59-64 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 46-53 8880916-4 1996 Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Tacrolimus 81-86 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 69-76 8880916-4 1996 Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Tacrolimus 81-86 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 69-76 8880916-4 1996 Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Tacrolimus 81-86 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 69-76 8880916-4 1996 Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Tacrolimus 81-86 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 69-76 21136324-4 1996 TARMD was found to be superior to conventional simulated-annealing methods, and produced structures that were conformationally similar to FK506 bound to wild-type FKBP-12. Tacrolimus 138-143 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 163-170 21232286-5 1996 The immunosuppressant drugs FK506 and rapamycin inhibit the prolyl isomerase activity of FKBP12 and could cause cardiac dysfunction by inducing a Ca(2+) leak from the sarcoplasmic reticulum. Tacrolimus 28-33 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 89-95 8627611-3 1996 Analyses of several X-ray crystal structures of FKBP12-urea complexes demonstrate that the urea-containing inhibitors associate with FKBP12 in a manner that is similar to, but significantly different from, that observed for the natural product FK506. Tacrolimus 244-249 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 48-54 8627611-3 1996 Analyses of several X-ray crystal structures of FKBP12-urea complexes demonstrate that the urea-containing inhibitors associate with FKBP12 in a manner that is similar to, but significantly different from, that observed for the natural product FK506. Tacrolimus 244-249 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 133-139 8785272-1 1996 The FK506-binding protein (FKBP12) is important in the immunosuppressant action of FK506 and rapamycin. Tacrolimus 4-9 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 27-33 8785272-5 1996 Results obtained for the FKBP12/rapamycin complex are similar to those found for the FKBP12/FK506 complex. Tacrolimus 92-97 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 85-91 8626235-2 1996 The antascomicins bind strongly to the FK506-binding protein FKBP12 and antagonize the immunosuppressive activity of FK506 and rapamycin. Tacrolimus 39-44 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 61-67 9005438-3 1996 For each mutant FKBP12, we measured the affinity for FK506 and rapamycin and the catalytic efficiency in the cis-frans peptidyl-prolyl isomerase reaction. Tacrolimus 53-58 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 16-22 9005438-4 1996 The mutation of Trp59 or Phe99 generates an FKBP12 with a significantly lower affinity for FK506 than wild-type protein. Tacrolimus 91-96 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 44-50 8545894-0 1995 Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506. Tacrolimus 68-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 28-34 8524402-0 1995 Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Tacrolimus 61-66 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 54-60 8524402-2 1995 CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). Tacrolimus 67-72 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 167-173 8524402-3 1995 We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. Tacrolimus 127-132 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 120-126 8524402-6 1995 In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. Tacrolimus 14-19 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 7-13 8524402-7 1995 The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein. Tacrolimus 30-35 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 23-29 8521476-1 1995 The immunosuppressant drug FK506 binds to the immunophilin protein FKBP12 and inhibits its prolyl isomerase activity. Tacrolimus 27-32 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 67-73 8521476-4 1995 FKBP12 is physically associated with the RyR and IP3R Ca2+ channels in the absence of FK506, with added FK506 disrupting these complexes. Tacrolimus 104-109 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 8521476-6 1995 We now report that calcineurin is physiologically associated with the IP3R-FKBP12 and RyR-FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or rapamycin. Tacrolimus 162-167 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 75-81 8521476-6 1995 We now report that calcineurin is physiologically associated with the IP3R-FKBP12 and RyR-FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or rapamycin. Tacrolimus 162-167 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 90-96 8545894-1 1995 To evaluate the roles of extracellular FKBP12, we examined the effect of extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and clinically. Tacrolimus 131-136 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 87-93 8545894-2 1995 The ability of FK506 to suppress phytohemagglutinin-induced proliferative response of human peripheral blood mononuclear cells was inhibited in the presence of recombinant FKBP12 dose-dependently. Tacrolimus 15-20 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 172-178 8545894-3 1995 We measured plasma levels of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34 patients receiving FK506 after liver transplantation. Tacrolimus 126-131 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 29-35 8545894-9 1995 These results suggest that the rapid increase in plasma levels of FKBP12 may contribute to the occurrence and progress of acute cellular rejection probably by inhibiting the immunosuppressive activity of FK506. Tacrolimus 204-209 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 66-72 8563622-0 1995 Structure comparison of native and mutant human recombinant FKBP12 complexes with the immunosuppressant drug FK506 (tacrolimus). Tacrolimus 109-114 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 60-66 8563622-0 1995 Structure comparison of native and mutant human recombinant FKBP12 complexes with the immunosuppressant drug FK506 (tacrolimus). Tacrolimus 116-126 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 60-66 8563622-2 1995 Here, we examine the effects of "conservative" and "nonconservative" substitutions on the X-ray crystal structures of human recombinant FKBP12 mutants in complex with the immunosuppressant drug FK506 (tacrolimus). Tacrolimus 194-199 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 136-142 8563622-2 1995 Here, we examine the effects of "conservative" and "nonconservative" substitutions on the X-ray crystal structures of human recombinant FKBP12 mutants in complex with the immunosuppressant drug FK506 (tacrolimus). Tacrolimus 201-211 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 136-142 7543369-0 1995 X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Tacrolimus 86-91 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 79-85 7543369-1 1995 The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. Tacrolimus 126-131 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 87-93 7642551-2 1995 The 12- and 13-kDa FK506 binding proteins (FKBP12 and FKBP13) are cis-trans peptidyl-prolyl isomerases that bind the macrolides FK506 (Tacrolimus) and rapamycin (Sirolimus). Tacrolimus 19-24 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 43-49 7642551-2 1995 The 12- and 13-kDa FK506 binding proteins (FKBP12 and FKBP13) are cis-trans peptidyl-prolyl isomerases that bind the macrolides FK506 (Tacrolimus) and rapamycin (Sirolimus). Tacrolimus 128-133 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 43-49 7642551-2 1995 The 12- and 13-kDa FK506 binding proteins (FKBP12 and FKBP13) are cis-trans peptidyl-prolyl isomerases that bind the macrolides FK506 (Tacrolimus) and rapamycin (Sirolimus). Tacrolimus 135-145 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 43-49 7642551-3 1995 The FKBP12.FK506 complex is immunosuppressive, acting as an inhibitor of the protein phosphatase calcineurin. Tacrolimus 11-16 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 4-10 7642551-6 1995 Mutations at FKBP12 residues Asp-37, Arg-42, His-87, and Ile-90 decrease calcineurin affinity of the mutant FKBP12.FK506 complex by as much as 2600-fold in the case of I90K. Tacrolimus 115-120 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 13-19 7642551-6 1995 Mutations at FKBP12 residues Asp-37, Arg-42, His-87, and Ile-90 decrease calcineurin affinity of the mutant FKBP12.FK506 complex by as much as 2600-fold in the case of I90K. Tacrolimus 115-120 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 108-114 7642551-7 1995 Replacement of three FKBP13 surface residues (Gln-50, Ala-95, and Lys-98) with the corresponding homologous FKBP12 residues (Arg-42, His-87, and Ile-90) generates an FKBP13 variant that is equivalent to FKBP12 in its affinity for FK506, rapamycin, and calcineurin. Tacrolimus 230-235 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 108-114 7543369-1 1995 The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. Tacrolimus 147-157 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 87-93 7543369-2 1995 In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active site on calcineurin A that is more than 10 A removed. Tacrolimus 29-34 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 22-28 7543369-3 1995 Instead, FKBP12-FK506 is so positioned that it can inhibit the dephosphorylation of its macromolecular substrates by physically hindering their approach to the active site. Tacrolimus 16-21 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 9-15 7543369-4 1995 The ternary complex described here represents the three-dimensional structure of a Ser/Thr protein phosphatase and provides a structural basis for understanding calcineurin inhibition by FKBP12-FK506. Tacrolimus 194-199 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 187-193 15299838-2 1995 FK506, in complex with its 12 kDa cytosolic receptor (FKBP12), is a potent agonist of immunosuppression through the inhibition of the phosphatase activity of calcineurin. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 54-60 7541044-0 1995 Interaction of FKBP12-FK506 with calcineurin A at the B subunit-binding domain. Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 15-21 7541044-6 1995 Furthermore, calcineurin A subunit mutants of residues Thr351, Leu354, and Lys360 showed NF kappa B transactivation activity and phosphatase activity with increased resistance to FKBP12-FK506 but displayed no or minimal increase in resistance for cyclosporin A inhibition. Tacrolimus 186-191 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 179-185 7541044-7 1995 Together, these results strongly suggest that the B subunit-binding domain is required for calcineurin activity intracellulary and interacts with the FKBP12-FK506 complex. Tacrolimus 157-162 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 150-156 7538591-0 1995 Determination of the differential effects of hydrogen bonding and water release on the binding of FK506 to native and Tyr82-->Phe82 FKBP-12 proteins using free energy simulations. Tacrolimus 98-103 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 135-142 7538591-1 1995 We use the thermodynamic integration technique to calculate the free energy associated with the Tyr82-->Phe82 mutation (Y82F) in the protein FKBP-12, both free and bound to known inhibitor FK506 (tacrolimis). Tacrolimus 192-197 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 144-151 7537219-5 1995 The amino acids in human FKBP12 which are proposed to be important for FK506 interaction are conserved in the schistosome protein. Tacrolimus 71-76 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 25-31 15299838-3 1995 Rapamycin (sirolimus), which is itself an immunosuppressant by a different mechanism, completes with FK506 for binding to FKBP12 and thereby acts as an antagonist of calcineurin inhibition. Tacrolimus 101-106 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 122-128 15299838-4 1995 We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. Tacrolimus 86-91 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 49-55 15299838-4 1995 We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. Tacrolimus 86-91 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 63-69 15299839-0 1995 Design, synthesis and structure of non-macrocyclic inhibitors of FKBP12, the major binding protein for the immunosuppressant FK506. Tacrolimus 125-130 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 65-71 15299839-1 1995 We have synthesized a series of non-macrocyclic ligands to FKBP12 that are comparable in binding potency and peptidyl prolyl isomerase (PPIase) inhibition to FK506 itself. Tacrolimus 158-163 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 59-65 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 14-19 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 7-13 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 14-19 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 300-307 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 58-63 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 7-13 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 58-63 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 300-307 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 58-63 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 7-13 15299839-5 1995 In the FKBP12-FK506 complex, a significant portion of the FK506 ligand, its "effector domain", projects beyond the envelope of the binding protein in a manner that is suggestive of a potential interaction with a second protein, the calcium-dependent phosphatase, calcineurin, whose inhibition by the FKBP 12-FK506 complex interrupts the T-cell activation events leading to immunosuppression. Tacrolimus 58-63 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 300-307 7531689-2 1995 FKBP-12 (FKBP), the soluble receptor for the immunosuppresant drug FK-506, is tightly bound to the calcium release channel (CRC)/ryanodine receptor (RyR) of skeletal muscle terminal cisternae (TC) of sarcoplasmic reticulum with a stoichiometry of 4 mol of FKBP per tetrameric RyR complex. Tacrolimus 67-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-7 7531689-2 1995 FKBP-12 (FKBP), the soluble receptor for the immunosuppresant drug FK-506, is tightly bound to the calcium release channel (CRC)/ryanodine receptor (RyR) of skeletal muscle terminal cisternae (TC) of sarcoplasmic reticulum with a stoichiometry of 4 mol of FKBP per tetrameric RyR complex. Tacrolimus 67-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-4 7531689-2 1995 FKBP-12 (FKBP), the soluble receptor for the immunosuppresant drug FK-506, is tightly bound to the calcium release channel (CRC)/ryanodine receptor (RyR) of skeletal muscle terminal cisternae (TC) of sarcoplasmic reticulum with a stoichiometry of 4 mol of FKBP per tetrameric RyR complex. Tacrolimus 67-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 9-13 7529414-4 1995 They interrupt the cytoplasmic portion of T-cell signaling by forming a complex with a binding protein--FKBP12 in the case of FK506 and rapamycin and cyclophilin A (CyPA) in the case of cyclosporin A (CsA). Tacrolimus 126-131 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 104-110 7533090-7 1995 Increased expression of FKBP12 resulted in increased sensitivity to FK506 and rapamycin, as measured by inhibition of calcineurin activity and p70 S6 kinase activity, respectively. Tacrolimus 68-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 24-30 7533090-9 1995 Two distinct point mutations in FKBP12, one altering a hydrophobic residue within the drug-binding pocket and the other changing a charged surface residue of FKBP12, abrogated its ability to mediate sensitivity to FK506 and rapamycin. Tacrolimus 214-219 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 32-38 7533090-9 1995 Two distinct point mutations in FKBP12, one altering a hydrophobic residue within the drug-binding pocket and the other changing a charged surface residue of FKBP12, abrogated its ability to mediate sensitivity to FK506 and rapamycin. Tacrolimus 214-219 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 158-164 7533090-10 1995 These results establish that FKBP12 can mediate sensitivity to both FK506 and rapamycin in mammalian cells. Tacrolimus 68-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 29-35 7529995-5 1995 For FK506, the kinetics of inhibition of human 12 kDa cytosolic FKBP (FKBP12cy) were clearly dependent on time. Tacrolimus 4-9 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 70-76 7529995-9 1995 On the other hand, the kinetics and amplitudes of the inhibition of FKBP12cy varied significantly if rapamycin was used as an inhibitor instead of FK 506. Tacrolimus 147-153 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 68-74 7529414-7 1995 The existence of strong FK506-FKBP12 binding suggests that FK506 is mimicking some natural ligand for FKBP12. Tacrolimus 24-29 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 30-36 7529414-7 1995 The existence of strong FK506-FKBP12 binding suggests that FK506 is mimicking some natural ligand for FKBP12. Tacrolimus 24-29 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 102-108 7529175-1 1994 The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the phosphatase calcineurin. Tacrolimus 115-120 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 31-37 7529175-2 1994 With the yeast two hybrid system, we detect complexes between FKBP12 and the calcineurin A catalytic subunit in both the presence and absence of FK506. Tacrolimus 145-150 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 62-68 7529175-3 1994 Mutations in FKBP12 surface residues or the absence of the calcineurin B regulatory subunit perturb the FK506-dependent, but not the ligand-independent, FKBP12-calcineurin complex. Tacrolimus 104-109 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 13-19 7529739-1 1994 FKBP12 is an 11.8-kDa protein that binds the potent immunosuppressants FK506 and rapamycin. Tacrolimus 71-76 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 7529739-2 1994 When bound to FK506, FKBP12 forms an inhibitory complex with calcineurin and interferes with signal transduction in activated T lymphocytes. Tacrolimus 14-19 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 21-27 7520438-3 1994 The FKBP12.FK-506 complex inhibits calcineurin, a calcium-dependent phosphatase that is a component of the signal transduction pathway leading to early lymphokine gene transcription. Tacrolimus 11-17 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 4-10 7524662-0 1994 Solution structure of FK506 bound to the R42K, H87V double mutant of FKBP-12. Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 69-76 7524662-1 1994 The binding of the FK506/FKBP-12 complex to calcineurin (CN), its putative target for immunosuppression, involves recognition of solvent-exposed regions of the ligand as well as FKBP-12 residues near the active site. Tacrolimus 19-24 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 25-32 7524662-1 1994 The binding of the FK506/FKBP-12 complex to calcineurin (CN), its putative target for immunosuppression, involves recognition of solvent-exposed regions of the ligand as well as FKBP-12 residues near the active site. Tacrolimus 19-24 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 178-185 7524662-6 1994 This work reports the solution structure of 13C-labeled FK506 bound to R42K, H87V FKBP-12. Tacrolimus 56-61 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 82-89 7524662-10 1994 Comparison with the NMR structure of FK506 bound to wild-type FKBP-12 reveals that the R42K, H87V mutation causes the ligand backbone near C16 to move by 2.5 to 4.5 A, reorients 15-MeO by 90 degrees, and shifts 13-MeO by approximately 1.5 A. Tacrolimus 37-42 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 62-69 7522303-1 1994 The immunosuppressive action of the drug FK506 involves inhibition of calcineurin in T-lymphocytes by a complex of FK506 and an FK506 binding protein, FKBP12, a member of the immunophilin protein family. Tacrolimus 41-46 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 151-157 7522303-1 1994 The immunosuppressive action of the drug FK506 involves inhibition of calcineurin in T-lymphocytes by a complex of FK506 and an FK506 binding protein, FKBP12, a member of the immunophilin protein family. Tacrolimus 115-120 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 151-157 7687744-3 1993 We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. Tacrolimus 100-105 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 54-60 1383226-2 1992 FK-506 binds to a growing family of receptors termed FK-506-binding proteins (FKBPs), the most abundant being a 12-kDa cytosolic receptor, FKBP12. Tacrolimus 0-6 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 139-145 1383226-7 1992 The 110-kDa activity observed in brain extracts appears to be the FKBP12.FK-506.calcineurin (CaN) complex previously reported (Liu, J., Farmer, J., Lane, W., Friedman, J., Weissman, I., and Schreiber, S. (1991) Cell 66, 807-815) while the 110 kDa activity observed in JURKAT cells is a novel FK-506-binding protein. Tacrolimus 73-79 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 66-72 1383226-8 1992 Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. Tacrolimus 35-41 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 28-34 1383226-8 1992 Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. Tacrolimus 35-41 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 209-215 1383226-8 1992 Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. Tacrolimus 35-41 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 209-215 1383226-8 1992 Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. Tacrolimus 254-260 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 28-34 1375932-1 1992 Two FK506 binding proteins of molecular mass 12 kDa (FKBP12) and 13 kDa (FKBP13) have been identified as common cellular receptors of the immunosuppressants FK506 and rapamycin. Tacrolimus 4-9 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 53-59 1375932-1 1992 Two FK506 binding proteins of molecular mass 12 kDa (FKBP12) and 13 kDa (FKBP13) have been identified as common cellular receptors of the immunosuppressants FK506 and rapamycin. Tacrolimus 157-162 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 53-59 1375171-0 1992 Solution structure of FK506 bound to FKBP-12. Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 37-44 1375751-3 1992 Two largely nonpolar, immunosuppressive agents, FK506 and rapamycin, each bind with high affinity to a common hydrophobic pocket on a small peptidylproline cis-trans isomerase known as FK506 binding protein (FKBP-12) and inhibit its activity. Tacrolimus 48-53 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 208-215 1375751-4 1992 In an effort to elucidate the structural features of these ligands responsible for the observed energetics, we have undertaken an investigation of the thermodynamics of binding of FK506 and rapamycin to FKBP-12. Tacrolimus 180-185 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 203-210 1375751-6 1992 By analyzing the distribution of changes in solvent-accessible surface area upon binding of FK506 to FKBP-12 from crystallographic data, it is found that 99% of the net surface buried upon binding involves nonpolar groups. Tacrolimus 92-97 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 101-108 1375171-1 1992 The complex of the immunosuppressant FK506 bound to FKBP-12 has been studied in solution using 1H and inverse-detected 13C NMR methods. Tacrolimus 37-42 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 52-59 34809463-5 2021 To this end, we characterized high-resolution structures of the Mucor circinelloides FKBP12 bound to FK506 and of the Aspergillus fumigatus, M. circinelloides, and human FKBP12 proteins bound to the FK506 analog APX879, which exhibits enhanced selectivity for fungal pathogens. Tacrolimus 101-106 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 85-91 1716149-1 1991 FKBP-12, the major T-cell binding protein for the immunosuppressive agents FK506 and rapamycin, catalyzes the interconversion of the cis and trans rotamers of the peptidyl-prolyl amide bond of peptide and protein substrates. Tacrolimus 75-80 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-7 34809463-5 2021 To this end, we characterized high-resolution structures of the Mucor circinelloides FKBP12 bound to FK506 and of the Aspergillus fumigatus, M. circinelloides, and human FKBP12 proteins bound to the FK506 analog APX879, which exhibits enhanced selectivity for fungal pathogens. Tacrolimus 199-204 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 170-176 33894161-4 2021 We performed a high-throughput phenotypic screen and identified a series of FK506 analogs that act as potent BMP potentiators by sequestering FKBP12 from BMP type I receptors. Tacrolimus 76-81 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 142-148 31531197-1 2019 FKBP12 ligands such as FK506 have been shown to activate the BMP signaling pathway and facilitate tissue regeneration. Tacrolimus 23-28 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 32622856-2 2020 The original member of this family, FKBP12, is a well-known binding partner for the immunosuppressive drugs tacrolimus (FK506) and sirolimus (rapamycin). Tacrolimus 108-118 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 36-42 32622856-2 2020 The original member of this family, FKBP12, is a well-known binding partner for the immunosuppressive drugs tacrolimus (FK506) and sirolimus (rapamycin). Tacrolimus 120-125 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 36-42 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 20-25 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 48-54 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 20-25 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 103-109 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 20-25 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 103-109 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 97-102 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 48-54 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 97-102 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 103-109 33195437-5 2020 Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. Tacrolimus 97-102 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 103-109 33195437-8 2020 The current review highlights FK506/rapamycin-FKBP12 interactions with calcineurin/TOR kinase in human and fungi, and development of non-immunosuppressive analogs of FK506, rapamycin, and novel small molecules in inhibition of fungal calcineurin and TOR kinase. Tacrolimus 30-35 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 46-52 32661607-8 2020 Pre-exposure of RBCs to FKBP12 followed by exposure to tacrolimus significantly decreased tacrolimus distribution in RBCs in a concentration-dependent manner. Tacrolimus 90-100 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 24-30 32661607-9 2020 In addition, preincubation of tacrolimus with FKBP12 significantly reduced the rate of tacrolimus distribution in RBCs. Tacrolimus 30-40 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 46-52 32661607-9 2020 In addition, preincubation of tacrolimus with FKBP12 significantly reduced the rate of tacrolimus distribution in RBCs. Tacrolimus 87-97 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 46-52 32369692-10 2020 Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Tacrolimus 0-10 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 67-73 32369692-14 2020 FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. Tacrolimus 63-73 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 31537789-0 2019 Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents. Tacrolimus 23-28 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 29-35 30827938-5 2019 Further study showed that both FK506 and FKVP activate BMP signaling in multiple cell types through FKBP12 antagonism. Tacrolimus 31-36 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 100-106 31100260-3 2019 (2019) utilize FKBP12 ligand to demonstrate that wound healing effects of FK506 occur via activation of the BMP (bone morphogenic protein) signaling pathway. Tacrolimus 74-79 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 15-21 30181374-2 2018 In mammals, FK506 inhibits the calcineurin-nuclear factor of activated T cells (NFAT) pathway to prevent T-cell proliferation by forming a ternary complex with its binding protein, FKBP12, and calcineurin. Tacrolimus 12-17 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 181-187 27193181-8 2016 The effect of such mutations on the binding affinity of FK506-related ligands is relevant for assessing the thermodynamic forces regulating molecular recognition in FKBP12 inhibition. Tacrolimus 56-61 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 165-171 29131377-1 2018 FKBP12, known as FK506 binding protein, binds to immunosuppressive drug FK506, which must be taken by patients who received organ transplant. Tacrolimus 17-22 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 0-6 29131377-5 2018 Inhibiting FKBP12 by FK506 significantly increased the rate of 1-cell and fragmented embryos, greatly reduced the rate of 2-cell embryos during in vitro fertilization. Tacrolimus 21-26 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 11-17 28108248-10 2017 We herein demonstrated that the new FK506-immobilized beads specifically isolated more FKBP12 than the original beads, thereby proving our method to be applicable to target identification experiments. Tacrolimus 36-41 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 87-93 27193181-7 2016 Here we apply the technique to a real drug-receptor system, by satisfactorily reproducing the experimental dissociation free energies of FK506-related bulky ligands towards the native FKBP12 enzyme and by predicting the dissociation constants for the same ligands towards the mutant I56D. Tacrolimus 137-142 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 184-190 26073814-4 2015 The AFM biosensor presented herein utilises the endogen drug receptor, FKBP12, to quantify Tacrolimus levels. Tacrolimus 91-101 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 71-77 26561008-1 2015 The tight complexes FKBP12 forms with immunosuppressive drugs, such as FK506 and rapamycin, are frequently used as models for developing approaches to structure-based drug design. Tacrolimus 71-76 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 20-26 26322864-5 2015 Inspired by the natural product FK506, we designed molecules that have affinity for both FKBP12 and HIV protease. Tacrolimus 32-37 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 89-95 24846380-6 2014 Furthermore, we observed sirolimus (i.e., rapamycin)-inducible interactions between FRB and FKBP12 and a dose-dependent abolishment of such interactions by FK506, the ligand of FKBP12. Tacrolimus 156-161 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 92-98 25986568-2 2015 The prototype of this protein family, FKBP12, is the binding partner for immunosuppressive drugs FK506 and rapamycin. Tacrolimus 97-102 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 38-44 24471694-0 2015 The full electron structure of the FKBP12/FK506 complex. Tacrolimus 42-47 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 35-41 24471694-5 2015 The results indicate that the interactions occur only between the LUMOs of FKBP12 and the HOMO of FK506, not between the HOMOs of FKBP12 and the LUMO of FK506. Tacrolimus 98-103 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 75-81 24471694-7 2015 The electron structures of FKBP12/FK506 give us a clearer understanding of their interaction mechanism and will help us design new ligands of FKBP12. Tacrolimus 34-39 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 27-33 24471694-7 2015 The electron structures of FKBP12/FK506 give us a clearer understanding of their interaction mechanism and will help us design new ligands of FKBP12. Tacrolimus 34-39 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 142-148 24816588-6 2014 The effects were independent of extracellular TGF-beta as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-beta receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-beta receptor. Tacrolimus 193-203 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 222-228 24846380-6 2014 Furthermore, we observed sirolimus (i.e., rapamycin)-inducible interactions between FRB and FKBP12 and a dose-dependent abolishment of such interactions by FK506, the ligand of FKBP12. Tacrolimus 156-161 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 177-183 26579923-6 2014 The methodology is applied, with encouraging results, to the calculation of the absolute binding free energy of some FK506-related ligands of the peptidyl prolyl cis-trans isomerase protein (FKBP12) with known dissociation constants. Tacrolimus 117-122 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 191-197 23224428-3 2013 Human FKBP12 and some of its paralogues bind to different macrocyclic antibiotics such as FK506 or rapamycin and their derivatives. Tacrolimus 90-95 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 6-12 23989449-2 2013 In yeasts and animals, FKBP12 can interact with rapamycin and FK506 to form rapamycin-FKBP12 and FK506-FKBP12 complex, respectively. Tacrolimus 62-67 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 23-29 23989449-2 2013 In yeasts and animals, FKBP12 can interact with rapamycin and FK506 to form rapamycin-FKBP12 and FK506-FKBP12 complex, respectively. Tacrolimus 62-67 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 86-92 23989449-2 2013 In yeasts and animals, FKBP12 can interact with rapamycin and FK506 to form rapamycin-FKBP12 and FK506-FKBP12 complex, respectively. Tacrolimus 62-67 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 86-92 23989449-3 2013 In higher plants, FKBP12 protein lost its function to bind rapamycin and FK506. Tacrolimus 73-78 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 18-24 24092409-7 2013 We extend the studies to mammalian cells and examine the FK-506 inhibition of the rapamycin-induced association of FRB/FKBP12. Tacrolimus 57-63 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 119-125 21518964-0 2011 Tacrolimus-induced hypertension: what"s endothelial and hematopoietic FKBP12 got to do with it? Tacrolimus 0-10 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 70-76 21466465-4 2011 In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Tacrolimus 121-126 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 286-292 21466465-4 2011 In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Tacrolimus 171-176 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 286-292 21182472-4 2010 Of note, rapamycin and FK506 bind to FKBP12, and the resulting complexes interfere with distinct intracellular signaling pathways driven, respectively, by the mammalian target of rapamycin and calcineurin phosphatase. Tacrolimus 23-28 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 37-43 21182472-9 2010 Interestingly, derivatives of FK506 that have the same FKBP12-binding properties as FK506 but lack functional immunosuppressant activity, exert the same apoptotic effect as FK506 in chronic lymphocytic leukemia.These findings suggest that a direct FKBP inhibition represents a further mechanism of immunosuppressants." Tacrolimus 30-35 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 55-61 19361439-0 2009 Differential responses of the backbone and side-chain conformational dynamics in FKBP12 upon binding the transition-state analog FK506: implications for transition-state stabilization and target protein recognition. Tacrolimus 129-134 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 81-87 19361439-2 2009 The macrolide FK506 is a transition-state analog of the catalyzed reaction and displaces FKBP12 from its natural target proteins. Tacrolimus 14-19 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 89-95 19361439-3 2009 We compared the conformational exchange dynamics of the backbone and methyl-bearing side chains of FKBP12 in the free and FK506-bound states using NMR relaxation-dispersion experiments. Tacrolimus 122-127 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 99-105 19361439-5 2009 In FK506-bound FKBP12, the backbone is confined to a single conformation, while conformational exchange prevails for many methyl groups. Tacrolimus 3-8 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 15-21 18465874-8 2008 The presence in PfFKBD of Cys-106 and Ser-109 (substituting for His-87 and Ile-90, respectively, in human FKBP12), which are 4-5 A from the nearest atom of the FK506 compound, suggests possible routes for the rational design of analogues of FK506 with specific antiparasitic activity. Tacrolimus 160-165 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 106-112 19201607-5 2009 Utilization of the optimized spacer enable the monolithic material bearing FK506 to identify not only FKBP12 but FKBP52, calcineurin A and calcineurin B at silver stained level, while that without spacer had failed. Tacrolimus 75-80 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 102-108 18465874-7 2008 Compared to the human FKBP12-FK506 complex reported earlier, the structure reveals structural differences in the beta5-beta6 segment that lines the FK506 binding site. Tacrolimus 29-34 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 22-28 18465874-7 2008 Compared to the human FKBP12-FK506 complex reported earlier, the structure reveals structural differences in the beta5-beta6 segment that lines the FK506 binding site. Tacrolimus 148-153 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 22-28 18465874-8 2008 The presence in PfFKBD of Cys-106 and Ser-109 (substituting for His-87 and Ile-90, respectively, in human FKBP12), which are 4-5 A from the nearest atom of the FK506 compound, suggests possible routes for the rational design of analogues of FK506 with specific antiparasitic activity. Tacrolimus 241-246 FKBP prolyl isomerase 1A pseudogene 4 Homo sapiens 106-112