1h0v

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spinqualitylabelsall models 1h0v, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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 ... [(full description)]

About this Structure

1H0V is a [Single protein] structure of sequence from [Homo sapiens] with UN4 as [ligand]. Active as [Transferred entry: 2.7.11.1], with EC number [2.7.1.37]. Structure known Active Site: UN4. Full crystallographic information is available from [OCA].

Reference

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

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