1H0W

Human cyclin dependent protein kinase 2 in complex with the inhibitor 2-Amino-6-[cyclohex-3-enyl]methoxypurine

1H0W の概要

• エントリーDOI: 10.2210/pdb1h0w/pdb
• 関連するPDBエントリー: 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 1H0V 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1QMZ
• 分子名称: CELL DIVISION PROTEIN KINASE 2, 1-AMINO-6-CYCLOHEX-3-ENYLMETHYLOXYPURINE (3 entities in total)
• 機能のキーワード: transferase, protein kinase, cell cycle, phosphorylation, cell division, mitosis, inhibition
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34222.80

構造登録者

Gibson, A.E.,Arris, C.E.,Bentley, J.,Boyle, F.T.,Curtin, N.J.,Davies, T.G.,Endicott, J.A.,Golding, B.T.,Grant, S.,Griffin, R.J.,Jewsbury, P.,Johnson, L.N.,Mesguiche, V.,Newell, D.R.,Noble, M.E.M.,Tucker, J.A.,Whitfield, H.J. (登録日: 2002-06-27, 公開日: 2003-06-27, 最終更新日: 2023-12-13)

主引用文献

Gibson, A.E.,Arris, C.E.,Bentley, J.,Boyle, F.T.,Curtin, N.J.,Davies, T.G.,Endicott, J.A.,Golding, B.T.,Grant, S.,Griffin, R.J.,Jewsbury, P.,Johnson, L.N.,Mesguiche, V.,Newell, D.R.,Noble, M.E.M.,Tucker, J.A.,Whitfield, H.J.
Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O(6)-Substituted Guanine Derivatives
J.Med.Chem., 45:3381-, 2002

PubMed Abstract: 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.

PubMed: 12139449
DOI: 10.1021/JM020056Z

実験手法

X-RAY DIFFRACTION (2.1 Å)