1V0B

Crystal structure of the t198a mutant of pfpk5

Summary for 1V0B

• Entry DOI: 10.2210/pdb1v0b/pdb
• Related: 1LCH 1OB3
• Descriptor: CELL DIVISION CONTROL PROTEIN 2 HOMOLOG (2 entities in total)
• Functional Keywords: transferase, serine/threonine-protein kinase, atp-binding, phosphorylation, cdk
• Biological source: PLASMODIUM FALCIPARUM
• Cellular location: Cytoplasm: Q07785
• Total number of polymer chains: 2
• Total formula weight: 66026.29

Authors

Holton, S.,Merckx, A.,Burgess, D.,Doerig, C.,Noble, M.,Endicott, J. (deposition date: 2004-03-26, release date: 2004-03-31, Last modification date: 2024-11-13)

Primary citation

Holton, S.,Merckx, A.,Burgess, D.,Doerig, C.,Noble, M.,Endicott, J.
Structures of P. Falciparum Pfpk5 Test the Cdk Regulation Paradigm and Suggest Mechanisms of Small Molecule Inhibition
Structure, 11:1329-, 2003

PubMed Abstract: Plasmodium falciparum cell cycle regulators are promising targets for antimalarial drug design. We have determined the structure of PfPK5, the first structure of a P. falciparum protein kinase and the first of a cyclin-dependent kinase (CDK) not derived from humans. The fold and the mechanism of inactivation of monomeric CDKs are highly conserved across evolution. ATP-competitive CDK inhibitors have been developed as potential leads for cancer therapeutics. These studies have identified regions of the CDK active site that can be exploited to achieve significant gains in inhibitor potency and selectivity. We have cocrystallized PfPK5 with three inhibitors that target such regions. The sequence differences between PfPK5 and human CDKs within these inhibitor binding sites suggest that selective inhibition is an attainable goal. Such compounds will be useful tools for P. falciparum cell cycle studies, and will provide lead compounds for antimalarial drug development.

PubMed: 14604523
DOI: 10.1016/J.STR.2003.09.020

Experimental method

X-RAY DIFFRACTION (2.2 Å)