1v0p
From Proteopedia
Structure of P. falciparum PfPK5-Purvalanol B ligand complex
Structural highlights
FunctionCDK2H_PLAFK Serine/threonine-protein kinase (PubMed:8844681, PubMed:14604523). Involved in the control of the cell cycle (By similarity). Required for entry into S-phase and mitosis (By similarity). Probable component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II (By similarity). In schizonts, phosphorylates ORC1 resulting in its dissociation from DNA, relocalization to the cytoplasm and likely its degradation (By similarity).[UniProtKB:P04551][1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPlasmodium 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. Structures of P. falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition.,Holton S, Merckx A, Burgess D, Doerig C, Noble M, Endicott J Structure. 2003 Nov;11(11):1329-37. PMID:14604523[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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