1ob3

Structure of P. falciparum PfPK5

spinqualitylabelsall models 1ob3, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ob3 is a 2 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CDK2H_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] 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 PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA