1OGU

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 2-ARYLAMINO-4-CYCLOHEXYLMETHYL-5-NITROSO-6-AMINOPYRIMIDINE INHIBITOR

Summary for 1OGU

• Entry DOI: 10.2210/pdb1ogu/pdb
• 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 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1QMZ
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, 4-{[4-AMINO-6-(CYCLOHEXYLMETHOXY)-5-NITROSOPYRIMIDIN-2-YL]AMINO}BENZAMIDE, ... (5 entities in total)
• Functional Keywords: kinase, transferase, serine/threonine-protein kinase, atp-binding, cell cycle, cell division, mitosis, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: 1OGU
• Total number of polymer chains: 4
• Total formula weight: 129435.88

Authors

Pratt, D.J.,Endicott, J.A.,Noble, M.E.M. (deposition date: 2003-05-13, release date: 2003-09-02, Last modification date: 2023-12-13)

Primary citation

Sayle, K.L.,Bentley, J.,Boyle, F.T.,Calvert, A.H.,Cheng, Y.,Curtin, N.J.,Endicott, J.A.,Golding, B.T.,Hardcastle, I.R.,Jewsbury, P.,Mesguiche, V.,Newell, D.R.,Noble, M.E.M.,Parsons, R.J.,Pratt, D.J.,Wang, L.Z.,Griffin, R.J.
Structure-Based Design of 2-Arylamino-4-Cyclohexyl Methyl-5-Nitroso-6-Aminopyrimidine Inhibitors of Cyclin-Dependent Kinases 1 and 2
Bioorg.Med.Chem.Lett., 13:3079-, 2003

PubMed Abstract: A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.

PubMed: 12941338
DOI: 10.1016/S0960-894X(03)00651-6

Experimental method

X-RAY DIFFRACTION (2.6 Å)