1G5S

CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH THE INHIBITOR H717

Summary for 1G5S

• Entry DOI: 10.2210/pdb1g5s/pdb
• Descriptor: CELL DIVISION PROTEIN KINASE 2, 2-[TRANS-(4-AMINOCYCLOHEXYL)AMINO]-6-(BENZYL-AMINO)-9-CYCLOPENTYLPURINE (3 entities in total)
• Functional Keywords: protein-inhibitor complex, cell cycle-transferase complex, cell cycle/transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• Total number of polymer chains: 1
• Total formula weight: 34382.03

Authors

Dreyer, M.K.,Borcherding, D.R.,Dumont, J.A.,Peet, N.P.,Tsay, J.T.,Wright, P.S.,Bitonti, A.J.,Shen, J.,Kim, S.-H. (deposition date: 2000-11-02, release date: 2001-11-02, Last modification date: 2023-08-09)

Primary citation

Dreyer, M.K.,Borcherding, D.R.,Dumont, J.A.,Peet, N.P.,Tsay, J.T.,Wright, P.S.,Bitonti, A.J.,Shen, J.,Kim, S.H.
Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.
J.Med.Chem., 44:524-530, 2001

PubMed Abstract: Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.

PubMed: 11170642
DOI: 10.1021/jm001043t

Experimental method

X-RAY DIFFRACTION (2.61 Å)