PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 14761195-3 2004 Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. Adenosine Triphosphate 141-144 cyclin dependent kinase 5 Homo sapiens 78-82 18220519-7 2007 Several classes of potent chemical inhibitors for cdk5 have been identified but most are competitive with the ATP binding site, resulting in a lack of specificity among the other cyclin-dependent kinases as well as other ATP-dependent kinases. Adenosine Triphosphate 110-113 cyclin dependent kinase 5 Homo sapiens 50-54 18220519-8 2007 We are working to discover specific inhibitors that might disrupt the interaction of tau and cdk5 at sites other than the ATP binding site. Adenosine Triphosphate 122-125 cyclin dependent kinase 5 Homo sapiens 93-97 11604388-13 2001 For cdk5.GST-p25, the K(m, ATP) = 3.2 +/- 0.7 microm, K(m, peptide) = 1.6 +/- 0.3 microm, and alpha = 7.2 +/- 1.8. Adenosine Triphosphate 27-30 cyclin dependent kinase 5 Homo sapiens 4-8 12372407-3 2002 The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. Adenosine Triphosphate 70-73 cyclin dependent kinase 5 Homo sapiens 92-96 12112670-3 2002 A three-dimensional computer model of Cdk5-p25-ATP has been generated previously [Chou et al., Biochem Biophys Res Commun 1999;259:420-428], providing a structural basis for the study of the mechanisms of Cdk5 activation. Adenosine Triphosphate 47-50 cyclin dependent kinase 5 Homo sapiens 38-42 12112670-3 2002 A three-dimensional computer model of Cdk5-p25-ATP has been generated previously [Chou et al., Biochem Biophys Res Commun 1999;259:420-428], providing a structural basis for the study of the mechanisms of Cdk5 activation. Adenosine Triphosphate 47-50 cyclin dependent kinase 5 Homo sapiens 205-209 12112670-4 2002 To assess the predicted ATP and p25 binding domains at the N-terminal of Cdk5, two mutants of Cdk5 were prepared in which amino acids 9-15 (Delta9-15) or 9-47 (Delta9-47) were deleted. Adenosine Triphosphate 24-27 cyclin dependent kinase 5 Homo sapiens 73-77 11054815-9 2000 Among the MT-associated kinases, GSK3beta and cdk5 most readily contribute to the ATP-induced "AD-like" phosphorylation of tau. Adenosine Triphosphate 82-85 cyclin dependent kinase 5 Homo sapiens 46-50 10362524-4 1999 Based on this structural inference, a 3-dimensional model of the Cdk5-Nck5a*-ATP complex was derived from the X-ray structure of Cdk2-cyclinA-ATP complex. Adenosine Triphosphate 77-80 cyclin dependent kinase 5 Homo sapiens 65-69 10998059-2 2000 They were recently described as potent, ATP-competitive, inhibitors of the cell cycle regulating cyclin-dependent kinases (CDKs). Adenosine Triphosphate 40-43 cyclin dependent kinase 5 Homo sapiens 123-127 10362524-4 1999 Based on this structural inference, a 3-dimensional model of the Cdk5-Nck5a*-ATP complex was derived from the X-ray structure of Cdk2-cyclinA-ATP complex. Adenosine Triphosphate 142-145 cyclin dependent kinase 5 Homo sapiens 65-69 7592534-3 1995 Most of this phosphorylation and electrophoretic mobility shift, that occurred in the brain extract incubated with ATP, were inhibited by butyrolactone I, a specific inhibitor of cdc2 kinase and cdk5. Adenosine Triphosphate 115-118 cyclin dependent kinase 5 Homo sapiens 195-199 7592534-5 1995 cdk5 purified from porcine brain decreased the electrophoretic mobility of dephosphorylated tau by in vitro phosphorylation of tau to the level present in microtubules polymerized with ATP. Adenosine Triphosphate 185-188 cyclin dependent kinase 5 Homo sapiens 0-4 32660255-5 2021 The inhibition of Cdk5 also ameliorated mitochondrial dysfunction by decreasing ROS levels and cytochrome c release, while increasing ATP production. Adenosine Triphosphate 134-137 cyclin dependent kinase 5 Homo sapiens 18-22 34182065-12 2021 These new methods for recognizing CDK inhibitors may be used to create non-ATP-competitive agents that target CDK4, CDK5, and other CDKs that have been recognized as important therapeutic targets in Alzheimer"s disease treatment. Adenosine Triphosphate 75-78 cyclin dependent kinase 5 Homo sapiens 116-120 33931002-3 2021 The present study aims at identifying the selective inhibitors for ATP binding site in CDK proteins (CDK1, CDK2, CDK4, and CDK5) following a multi-target drug designing approach. Adenosine Triphosphate 67-70 cyclin dependent kinase 5 Homo sapiens 123-127 31163256-9 2019 Myricetin inhibited CDK5 activation by directly binding to its ATP-binding pocket. Adenosine Triphosphate 63-66 cyclin dependent kinase 5 Homo sapiens 20-24 32974274-3 2020 Since the successful discovery and development of Roscovitine, several ATP-competitive inhibitors of CDK5 and peptide inhibitors of CDK5/p25 interface have been developed. Adenosine Triphosphate 71-74 cyclin dependent kinase 5 Homo sapiens 101-105 32974274-7 2020 By implementing a fluorescent biosensor that discriminates against ATP-pocket binding compounds to screen for allosteric inhibitors that target conformational activation of CDK5, we have identified a novel family of quinazolinones. Adenosine Triphosphate 67-70 cyclin dependent kinase 5 Homo sapiens 173-177 32974274-9 2020 The quinazolinone derivatives described in this study are the first small molecules reported to target CDK5 at a site other than the ATP pocket, thereby constituting attractive leads for glioblastoma therapeutics and providing therapeutic perspectives for neurodegenerative diseases. Adenosine Triphosphate 133-136 cyclin dependent kinase 5 Homo sapiens 103-107 20491486-4 2010 Here, we report that a second Mg(2+) in addition to the one forming the MgATP complex is required to bind to cdk5/p25 for its catalytic activity. Adenosine Triphosphate 72-77 cyclin dependent kinase 5 Homo sapiens 109-113 31073393-5 2019 Structure-based pharmacophore investigated the essential complementary chemical features of ATP-binding site of Cdk5 in complex with roscovitine. Adenosine Triphosphate 92-95 cyclin dependent kinase 5 Homo sapiens 112-116 31073393-10 2019 The docking of candidate inhibitors filtered 10 molecules with docking score >80.00 and established polar and non-polar interactions with the ATP-binding site residues of Cdk5/p25. Adenosine Triphosphate 145-148 cyclin dependent kinase 5 Homo sapiens 174-178 31073393-12 2019 During 30 ns simulation, the candidate inhibitors established <3.0 A root mean square deviation and stable hydrogen bond interactions with the ATP-binding site residues of Cdk5/p25. Adenosine Triphosphate 146-149 cyclin dependent kinase 5 Homo sapiens 175-179 30079618-7 2018 Roscovitine, an ATP-competitive CDK5 inhibitor, disrupted localization of the expressed MBP peptide. Adenosine Triphosphate 16-19 cyclin dependent kinase 5 Homo sapiens 32-36 28868329-8 2017 Cdk5 is then incubated with histone H1, a well-established in vitro target of Cdk5, and [gamma-32P]ATP. Adenosine Triphosphate 99-102 cyclin dependent kinase 5 Homo sapiens 0-4 29856575-5 2016 In the second generation Cdk5 inhibitors, the ATP-binding pocket, a highly conserved site, has been targeted in the drug design in most cases. Adenosine Triphosphate 46-49 cyclin dependent kinase 5 Homo sapiens 25-29 25438765-0 2014 Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening. Adenosine Triphosphate 58-61 cyclin dependent kinase 5 Homo sapiens 78-82 25438765-7 2014 The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity. Adenosine Triphosphate 46-49 cyclin dependent kinase 5 Homo sapiens 66-70 24998602-4 2014 Docking studies were realized to determine the binding mode of the inhibitors into the ATP binding domain of the CDK5 catalytic site. Adenosine Triphosphate 87-90 cyclin dependent kinase 5 Homo sapiens 113-117 24704205-6 2014 Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Adenosine Triphosphate 129-132 cyclin dependent kinase 5 Homo sapiens 90-94 24704205-7 2014 Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination. Adenosine Triphosphate 221-224 cyclin dependent kinase 5 Homo sapiens 190-194 27481520-2 2013 Competitive inhibition of the ATP-binding pocket of CDK5 is involved in fighting with neurodegenerative diseases, diabetes, tumors, inflammations etc. Adenosine Triphosphate 30-33 cyclin dependent kinase 5 Homo sapiens 52-56 27481520-12 2013 These findings should provide insights into the inhibition mechanism of the CDK5/p25 complex and be useful for the rational design of novel ATP-binding competitive inhibitors in the near future. Adenosine Triphosphate 140-143 cyclin dependent kinase 5 Homo sapiens 76-80 31137734-9 2019 Molecular interactions analysis suggested that each inhibitor occupied the ATP-binding site of Cdk5/p25 and formed stable interactions. Adenosine Triphosphate 75-78 cyclin dependent kinase 5 Homo sapiens 95-99 24983862-6 2014 ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3beta where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. Adenosine Triphosphate 57-60 cyclin dependent kinase 5 Homo sapiens 80-84 24983862-6 2014 ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3beta where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. Adenosine Triphosphate 57-60 cyclin dependent kinase 5 Homo sapiens 90-94 21641213-3 2011 These results are substantiated using computer docking methods (DarwinDock/GenDock), which predict that Roscovitine and the triazole 7 bind to the ATP-binding site of CDK5/p25 with comparable binding energies, whereas the corresponding pentafluorophenylmethyl-triazole, 9, has dramatically reduced binding energy (in accordance with its lack of neuroprotection). Adenosine Triphosphate 147-150 cyclin dependent kinase 5 Homo sapiens 167-171 21681969-1 2011 The lack of selectivity of all existing ATP competitive inhibitors for a single cyclin-dependent kinase (CDK) has led us to redirect the structure-based molecule design from targeting the classic ATP-binding pocket in CDK5 toward the CDK5/p25 interface. Adenosine Triphosphate 40-43 cyclin dependent kinase 5 Homo sapiens 218-222 21681969-1 2011 The lack of selectivity of all existing ATP competitive inhibitors for a single cyclin-dependent kinase (CDK) has led us to redirect the structure-based molecule design from targeting the classic ATP-binding pocket in CDK5 toward the CDK5/p25 interface. Adenosine Triphosphate 196-199 cyclin dependent kinase 5 Homo sapiens 218-222 20491486-5 2010 It activates cdk5/p25 by demonstrating an increase in k(cat) and induces a conformational change that favors ATP binding but has no effect on the binding affinity for the H1P peptide substrate. Adenosine Triphosphate 109-112 cyclin dependent kinase 5 Homo sapiens 13-17 18636751-5 2008 We found that the cdk5/p25-catalyzed phosphorylation of tau follows a rapid equilibrium, random kinetic mechanism, as evidenced by initial velocity analysis indicating sequential addition of tau and ATP, and studies of the mechanism of inhibition by substrate analogue AMP, product ADP, and analogues of peptide substrate H1P. Adenosine Triphosphate 199-202 cyclin dependent kinase 5 Homo sapiens 18-22