1h0v

HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[(R)-PYRROLIDINO-5'-YL]METHOXYPURINE

spinqualitylabelsall models 1h0v, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1h0v is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: UN4 Related: 1aq1, 1b38, 1b39, 1buh, 1ckp, 1di8, 1dm2, 1e1v, 1e1x, 1e9h, 1f5q, 1fin, 1fq1, 1fvt, 1fvv, 1g5s, 1gih, 1gii, 1gij, 1gy3, 1gz8, 1h00, 1h01, 1h06, 1h07, 1h08, 1h0u, 1h0w, 1hck, 1hcl, 1jst, 1jsu, 1jsv, 1jvp, 1qmz Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed O(6)-substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Fifty-eight O(6)-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic O(6) substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O(6)-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site. Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives.,Gibson AE, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Whitfield HJ J Med Chem. 2002 Aug 1;45(16):3381-93. PMID:12139449 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2

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