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| | <StructureSection load='1v0p' size='340' side='right'caption='[[1v0p]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1v0p' size='340' side='right'caption='[[1v0p]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1v0p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V0P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1v0p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V0P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PVB:PURVALANOL+B'>PVB</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lch|1lch]], [[1ob3|1ob3]], [[1v0b|1v0b]], [[1v0o|1v0o]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PVB:PURVALANOL+B'>PVB</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v0p OCA], [https://pdbe.org/1v0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v0p RCSB], [https://www.ebi.ac.uk/pdbsum/1v0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v0p ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v0p OCA], [https://pdbe.org/1v0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v0p RCSB], [https://www.ebi.ac.uk/pdbsum/1v0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v0p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CDC2H_PLAFK CDC2H_PLAFK]] Plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into S-phase and mitosis. Component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II (By similarity).
| + | [https://www.uniprot.org/uniprot/CDK2H_PLAFK 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]<ref>PMID:14604523</ref> <ref>PMID:8844681</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plafa]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Burgess, D]] | + | [[Category: Burgess D]] |
| - | [[Category: Doerig, C]] | + | [[Category: Doerig C]] |
| - | [[Category: Endicott, J]] | + | [[Category: Endicott J]] |
| - | [[Category: Holton, S]] | + | [[Category: Holton S]] |
| - | [[Category: Merckx, A]] | + | [[Category: Merckx A]] |
| - | [[Category: Noble, M]] | + | [[Category: Noble M]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cdk]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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][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 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2003 Nov;11(11):1329-37. PMID:14604523
- ↑ Graeser R, Franklin RM, Kappes B. Mechanisms of activation of the cdc2-related kinase PfPK5 from Plasmodium falciparum. Mol Biochem Parasitol. 1996 Jul;79(1):125-7. PMID:8844681 doi:10.1016/0166-6851(96)02643-6
- ↑ 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. 2003 Nov;11(11):1329-37. PMID:14604523
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