PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20806954-9 2010 The hydrogen bonds formed between the INH peptide, residues Tyr1, Tyr3, and Leu7 with the BACE1 residues Leu267, Cys269, Trp270, Asp311, and Asp 317 can strengthen the binding of the BACE1-INH complex. Aspartic Acid 129-132 beta-secretase 1 Homo sapiens 90-95 21500352-1 2011 BACE1 cleaves the amyloid precursor protein (APP) at the beta-cleavage site (Met(671) -Asp(672) ) to initiate the generation of amyloid peptide Abeta. Aspartic Acid 87-90 beta-secretase 1 Homo sapiens 0-5 21183353-4 2011 The most potent inhibitor, tert-alcohol containing (R)-12 (IC(50)=0.19muM) was co-crystallized in the active site of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal amine makes a hydrogen bond to one of the catalytic aspartic acids. Aspartic Acid 246-260 beta-secretase 1 Homo sapiens 121-127 20806954-9 2010 The hydrogen bonds formed between the INH peptide, residues Tyr1, Tyr3, and Leu7 with the BACE1 residues Leu267, Cys269, Trp270, Asp311, and Asp 317 can strengthen the binding of the BACE1-INH complex. Aspartic Acid 129-132 beta-secretase 1 Homo sapiens 183-188 17112725-1 2007 BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Aspartic Acid 100-110 beta-secretase 1 Homo sapiens 0-6 20043700-3 2010 NMR data and the crystal structure revealed that this hit makes H-bond interactions with the two catalytic aspartates, occupies the nonprime side region of the active site of BACE-1, and extends toward the S3 subpocket (S3sp). Aspartic Acid 107-117 beta-secretase 1 Homo sapiens 175-181 19854048-3 2009 Docking studies suggest these inhibitors may bind within the BACE-1 active site through H-bonding interactions involving the catalytic aspartate residues. Aspartic Acid 135-144 beta-secretase 1 Homo sapiens 61-67 19013073-4 2008 Compound 33d, which displayed the highest BACE 1 activity (18.33+/-2.80 micromol/L) among these two series, was chosen to study the protein binding pattern and the result showed that it was in close contact with two essential catalytic aspartates (Asp32 and Asp228) of the BACE 1. Aspartic Acid 236-246 beta-secretase 1 Homo sapiens 42-48 18811140-2 2008 An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Aspartic Acid 125-135 beta-secretase 1 Homo sapiens 34-40 18378702-6 2008 We further describe the crystal structure of the dehydrated form of BACE1, showing that BACE1 activity is dependent on the dynamics of a catalytically required Asp-bound water molecule, which directly affects its catalytic properties. Aspartic Acid 160-163 beta-secretase 1 Homo sapiens 68-73 18378702-6 2008 We further describe the crystal structure of the dehydrated form of BACE1, showing that BACE1 activity is dependent on the dynamics of a catalytically required Asp-bound water molecule, which directly affects its catalytic properties. Aspartic Acid 160-163 beta-secretase 1 Homo sapiens 88-93 17685503-2 2007 X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). Aspartic Acid 126-140 beta-secretase 1 Homo sapiens 144-150 17685503-2 2007 X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). Aspartic Acid 152-155 beta-secretase 1 Homo sapiens 144-150 17685503-2 2007 X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). Aspartic Acid 161-164 beta-secretase 1 Homo sapiens 144-150 20620068-5 2010 The most effective BACE 1 inhibitor 9f (27.85+/-2.46 micromol/L) was selected for further receptor-binding studies, the result of which indicated that an essential hydrogen bonds was formed between the urea group of 9f and the catalytic aspartate Asp228. Aspartic Acid 237-246 beta-secretase 1 Homo sapiens 19-25 20097169-2 2010 To study the enzymatic function of BACE, we mutated either of the two aspartic acid residues in the active site of BACE. Aspartic Acid 70-83 beta-secretase 1 Homo sapiens 35-39 20097169-2 2010 To study the enzymatic function of BACE, we mutated either of the two aspartic acid residues in the active site of BACE. Aspartic Acid 70-83 beta-secretase 1 Homo sapiens 115-119 20097169-4 2010 In contrast, substituting both active site aspartic acid residues produced a functionally inactive, endoplasmic reticulum-retained and partially glycosylated BACE. Aspartic Acid 43-56 beta-secretase 1 Homo sapiens 158-162 19547991-1 2009 It is well established that only a fraction of Abeta peptides in the brain of Alzheimer"s disease (AD) patients start with N-terminal aspartate (Abeta(1D)) which is generated by proteolytic processing of amyloid precursor protein (APP) by BACE. Aspartic Acid 134-143 beta-secretase 1 Homo sapiens 239-243 19284778-3 2009 For one such hit class, defined by a central aminobenzylpiperidine (ABP) moiety, X-ray crystal structures of BACE mutant-disulfide conjugates revealed that the fragment bound by engaging both catalytic aspartates with hydrogen bonds. Aspartic Acid 202-212 beta-secretase 1 Homo sapiens 109-113 18979630-11 2008 While cathepsin B is more effective than BACE-1 in processing the Asp-containing peptide derivatives, only cathepsin B can cleave the isoAsp-containing peptides, which occurs with high catalytic efficiency. Aspartic Acid 66-69 beta-secretase 1 Homo sapiens 41-47 11922623-5 2002 Comparison of the computed structure of pro-BACE with X-ray structures of pepsinogen and progastricsin (two other pro-aspartyl proteases) reveals a significant difference in the relationship of the pro-segment to the catalytic aspartates. Aspartic Acid 227-237 beta-secretase 1 Homo sapiens 44-48 16451048-4 2006 A three-dimensional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE inhibitors. Aspartic Acid 140-150 beta-secretase 1 Homo sapiens 59-65 15809332-5 2005 Each protein contained a pair of active site motifs (Asp/Thr or Ser/Gly), which is a common characteristic of aspartic proteases including BACE1. Aspartic Acid 53-56 beta-secretase 1 Homo sapiens 139-144 12458195-11 2003 We propose that a conformational change related to the reprotonation of aspartates during or after the bond-breaking event is the rate-limiting segment in the catalytic reaction of beta-amyloid precursor protein-cleaving enzyme, and ligands binding to other than the ground-state forms of the enzyme might provide inhibitors of greater pharmacological relevance. Aspartic Acid 72-82 beta-secretase 1 Homo sapiens 181-227 15522224-6 2004 Mutagenesis of the identified cleavage sites revealed that the mutants D379A, D379L or D379E block the degradation of BACE into the approximately 12kDa product, confirming the importance of Asp(379). Aspartic Acid 190-193 beta-secretase 1 Homo sapiens 118-122 15456259-2 2004 There are two aspartic acid residues (Asp 32 and Asp 228) present in the catalytic region of BACE that can adopt multiple protonation states. Aspartic Acid 14-27 beta-secretase 1 Homo sapiens 93-97 15456259-2 2004 There are two aspartic acid residues (Asp 32 and Asp 228) present in the catalytic region of BACE that can adopt multiple protonation states. Aspartic Acid 38-41 beta-secretase 1 Homo sapiens 93-97 15456259-2 2004 There are two aspartic acid residues (Asp 32 and Asp 228) present in the catalytic region of BACE that can adopt multiple protonation states. Aspartic Acid 49-52 beta-secretase 1 Homo sapiens 93-97 14692784-3 2003 Two independent molecular dynamics (MD) simulations of BACE in complex with the potent inhibitor OM99-2 are carried out to determine the preferred protonation state of the Asp diad in the context that is consistent with the previous X-ray crystal structure. Aspartic Acid 172-175 beta-secretase 1 Homo sapiens 55-59 11716984-4 2001 In this study, we demonstrate that overexpression of human beta-secretase (BACE-1) in HEK293 cells resulted in predominant Abeta cleavage at position Glu(11) rather than Asp(1), as well as increased production of Abeta(x)-34, but not Abeta(x)-40. Aspartic Acid 170-173 beta-secretase 1 Homo sapiens 75-81 21647837-5 2012 Crucial to this achievement were the initial identification of a ligand-efficient isothiourea fragment through target-based NMR screening and the determination of its X-ray crystal structure in complex with BACE-1, which revealed an extensive H-bond network with the two active site aspartate residues. Aspartic Acid 283-292 beta-secretase 1 Homo sapiens 207-213 10677483-9 2000 Alignment of cleavage site sequences of peptides indicates that the specificity of memapsin 2 resides mainly at the S(1)" subsite, which prefers small side chains such as Ala, Ser, and Asp. Aspartic Acid 185-188 beta-secretase 1 Homo sapiens 83-93 32890999-7 2020 A molecular docking study supported this result, showing a good interaction of the amino group with aspartic acid residues of the catalytic diade of BACE-1. Aspartic Acid 100-113 beta-secretase 1 Homo sapiens 149-155 34280745-6 2021 The intercalation of Asp2- and CO32- caused 003 peaks in XRD sharper and d003 decreased from 8.15 A to 7.70 A which is assigned to Ca2Al-LDH(Asp, CO3). Aspartic Acid 141-144 beta-secretase 1 Homo sapiens 21-25 33007563-7 2020 In silico molecular docking and dynamics simulation studies of leads suggested their consensual binding affinity toward PAS-AChE in addition to aspartate dyad of BACE-1. Aspartic Acid 144-153 beta-secretase 1 Homo sapiens 162-168 31491074-10 2019 The in silico molecular docking and dynamics simulation studies of lead compounds affirmed their consensual binding interactions with PAS-AChE and aspartate dyad of BACE-1. Aspartic Acid 147-156 beta-secretase 1 Homo sapiens 165-171 30648708-4 2019 A combined study using potentiometric and spectroscopic (UV-Vis, CD, EPR and NMR) techniques indicates the formation of the wanted major species, [CuH(ONMe-Asp)]2+, where copper(ii) is bound to His4(Nepsilon), His7(Nepsilon), His9(Nepsilon) and Asp2(COO-). Aspartic Acid 156-159 beta-secretase 1 Homo sapiens 245-249 28710924-3 2017 There are two catalytic aspartates (ASP32 and ASP228) presents in the active domain of BACE1. Aspartic Acid 24-34 beta-secretase 1 Homo sapiens 87-92 28370344-7 2017 The acidic and basic components of the BACE1 catalytic dyad are clear, while either aspartic acid of the CatD catalytic dyad could play the role of acid or base. Aspartic Acid 84-97 beta-secretase 1 Homo sapiens 39-44 27816517-2 2016 The co-crystal structure of a representative thiazinamine 2e bound with the BACE1 active site displayed a binding mode driven by interactions with the catalytic aspartate dyad and engagement of the biaryl amide toward the S1 and S3 pockets. Aspartic Acid 161-170 beta-secretase 1 Homo sapiens 76-81 27474865-2 2016 There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Aspartic Acid 24-34 beta-secretase 1 Homo sapiens 78-83 26085383-5 2015 The interaction of both mono- and dinuclear complexes with very similar dicarboxylates of biological interest (malate and aspartate) resulted in strikingly different outcomes: in the first case a ternary complex [ligand...metal...dicarboxylate] was obtained almost quantitatively, while in the latter, the Cu(ii) displacement to form Cu(Asp)2 was predominant. Aspartic Acid 122-131 beta-secretase 1 Homo sapiens 334-342 23640428-4 2013 The pK a values of the BACE-1 acidic residues deviate substantially from the estimates for model compounds in solution and display a ligand dependent variability, especially in the case of the catalytic Asp dyad residues. Aspartic Acid 203-206 beta-secretase 1 Homo sapiens 23-29 22545704-1 2012 In this molecular docking study, the protonation states of the catalytic Asp dyad of the beta-secretase (BACE1) enzyme in the presence of eight chemically diverse inhibitors have been predicted. Aspartic Acid 73-76 beta-secretase 1 Homo sapiens 105-110 22545704-6 2012 These results show that the knowledge of a single protonation state of the Asp dyad is not sufficient to search for the novel inhibitors of BACE1 and the most plausible state for each inhibitor must be determined prior to conducting in-silico screening. Aspartic Acid 75-78 beta-secretase 1 Homo sapiens 140-145 28359674-2 2017 A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1 enzyme, resulting in the identification of a thiolactam-containing hit compound possessing IC50 in the low micromolar range, and confirming the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues. Aspartic Acid 368-381 beta-secretase 1 Homo sapiens 119-124 28040476-1 2017 The affinity of ligands for G-protein-coupled receptors (GPCRs) is allosterically regulated by Na+ via a highly conserved aspartate residue (Asp2.50) in the second transmembrane domain of GPCRs. Aspartic Acid 122-131 beta-secretase 1 Homo sapiens 141-145 27111489-2 2016 Two aspartic acid residues are present in the BACE1 catalytic region which can adopt multiple protonation states depending on the chemical nature of its inhibitors, i.e., monoprotonated, diprotonated and di-deprotonated states. Aspartic Acid 4-17 beta-secretase 1 Homo sapiens 46-51 25345508-10 2014 In the case of "levomilnacipran-BACE1" interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. Aspartic Acid 101-114 beta-secretase 1 Homo sapiens 32-37 25345508-10 2014 In the case of "levomilnacipran-BACE1" interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. Aspartic Acid 101-114 beta-secretase 1 Homo sapiens 127-133 23465612-0 2013 Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates. Aspartic Acid 103-113 beta-secretase 1 Homo sapiens 52-58