2UZE

Crystal structure of human CDK2 complexed with a thiazolidinone inhibitor

Summary for 2UZE

• Entry DOI: 10.2210/pdb2uze/pdb
• Related: 1E9H 1FIN 1FVV 1GY3 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1JST 1JSU 1OGU 1OI9 1OIU 1OIY 1OKV 1OKW 1OL1 1OL2 1P5E 1PKD 1QMZ 1URC 1VYW 2BKZ 2BPM 2C4G 2C5N 2C5O 2C5P 2C5T 2C5V 2C5X 2C6T 2CCH 2CCI 2CJM 2IW6 2IW8 2IW9 2UUE 2UZB 2UZD 2UZL 2UZN 2UZO
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, 4-{5-[(Z)-(2-IMINO-4-OXO-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]FURAN-2-YL}BENZOIC ACID, ... (4 entities in total)
• Functional Keywords: transferase, atp-binding, phosphorylation, cdk2, kinase, cyclin, mitosis, cell cycle, cell division, nucleotide-binding, serine/threonine-protein kinase, thiazolidinone ligand
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 127990.16

Authors

Richardson, C.M.,Dokurno, P.,Murray, J.B.,Surgenor, A.E. (deposition date: 2007-04-27, release date: 2007-06-26, Last modification date: 2024-11-06)

Primary citation

Richardson, C.M.,Nunns, C.L.,Williamson, D.S.,Parratt, M.J.,Dokurno, P.,Howes, R.,Borgognoni, J.,Drysdale, M.J.,Finch, H.,Hubbard, R.E.,Jackson, P.S.,Kierstan, P.,Lentzen, G.,Moore, J.D.,Murray, J.B.,Simmonite, H.,Surgenor, A.E.,Torrance, C.J.
Discovery of a Potent Cdk2 Inhibitor with a Novel Binding Mode, Using Virtual Screening and Initial, Structure-Guided Lead Scoping.
Bioorg.Med.Chem.Lett., 17:3880-, 2007

PubMed Abstract: Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.

PubMed: 17570665
DOI: 10.1016/J.BMCL.2007.04.110

Experimental method

X-RAY DIFFRACTION (2.4 Å)