1PXI

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 4-(2,5-Dichloro-thiophen-3-yl)-pyrimidin-2-ylamine

Summary for 1PXI

• Entry DOI: 10.2210/pdb1pxi/pdb
• Related: 1AQ1 1B39 1CKP 1DI8 1DM2 1E1V 1E1X 1E9H 1FIN 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GZ8 1HCK 1HCL 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9
• Descriptor: Cell division protein kinase 2, 4-(2,5-DICHLOROTHIEN-3-YL)PYRIMIDIN-2-AMINE (3 entities in total)
• Functional Keywords: protein kinase, cell cycle, phosphorylation, cell division, mitosis, inhibition, transferase, serine/threonine-protein kinase, atp-binding, 3d-structure.
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 34222.60

Authors

Wu, S.Y.,McNae, I.,Kontopidis, G.,McClue, S.J.,McInnes, C.,Stewart, K.J.,Wang, S.,Zheleva, D.I.,Marriage, H.,Lane, D.P.,Taylor, P.,Fischer, P.M.,Walkinshaw, M.D. (deposition date: 2003-07-04, release date: 2003-12-09, Last modification date: 2023-08-16)

Primary citation

Wu, S.Y.,McNae, I.,Kontopidis, G.,McClue, S.J.,McInnes, C.,Stewart, K.J.,Wang, S.,Zheleva, D.I.,Marriage, H.,Lane, D.P.,Taylor, P.,Fischer, P.M.,Walkinshaw, M.D.
Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop
Structure, 11:399-410, 2003

PubMed Abstract: A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds was discovered with the new database-mining program LIDAEUS through in silico screening. Four compounds with IC(50) values ranging from 17 to 0.9 microM were selected for X-ray crystal analysis. Two distinct binding modes are observed, one of which resembles the hydrogen bonding pattern of bound ATP. In the second binding mode, the ligands trigger a conformational change in the activation T loop by inducing movement of Lys(33) and Asp(145) side chains. The family of molecules discovered provides an excellent starting point for the design and synthesis of tight binding inhibitors, which may lead to a new class of antiproliferative drugs.

PubMed: 12679018
DOI: 10.1016/S0969-2126(03)00060-1

Experimental method

X-RAY DIFFRACTION (1.95 Å)