5xvu: Difference between revisions

Latest revision as of 08:15, 22 November 2023

Crystal structure of the protein kinase CK2 catalytic domain from Plasmodium falciparum bound to ATP

Structural highlights

5xvu is a 3 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	ATP, CL, EDO, PEG, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8IIR9_PLAF7

Publication Abstract from PubMed

Malaria causes every year over half-a-million deaths. The emergence of parasites resistant to available treatments makes the identification of new targets and their inhibitors an urgent task for the development of novel anti-malaria drugs. Protein kinase CK2 is an evolutionary-conserved eukaryotic serine/threonine protein kinase that in Plasmodium falciparum (PfCK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of PfCK2alpha (D179S inactive single mutant) in complex with ATP at a resolution of 3.0 A. Compared to the human enzyme, the structure reveals a subtly altered ATP binding pocket comprising five substitutions in the vicinity of the adenine base, that together with potential allosteric sites, could be exploited to design novel inhibitors specifically targeting the Plasmodium enzyme. We provide evidence for the dual autophosphorylation of residues Thr(63) and Tyr(30) of PfCK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against PfCK2 with an IC50 of 13.2 nM.

The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition.,Ruiz-Carrillo D, Lin J, El Sahili A, Wei M, Sze SK, Cheung PCF, Doerig C, Lescar J Sci Rep. 2018 May 9;8(1):7365. doi: 10.1038/s41598-018-25738-5. PMID:29743645^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ruiz-Carrillo D, Lin J, El Sahili A, Wei M, Sze SK, Cheung PCF, Doerig C, Lescar J. The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition. Sci Rep. 2018 May 9;8(1):7365. doi: 10.1038/s41598-018-25738-5. PMID:29743645 doi:https://dx.doi.org/10.1038/s41598-018-25738-5

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Ruiz-Carrillo D, Lin J, El Sahili A, Wei M, Sze SK, Cheung PCF, Doerig C, Lescar J. The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition. Sci Rep. 2018 May 9;8(1):7365. doi: 10.1038/s41598-018-25738-5. PMID:29743645 doi:https://dx.doi.org/10.1038/s41598-018-25738-5

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5xvu' size='340' side='right'caption='[[5xvu]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XVU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XVU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF11_0096, PF3D7_1108400 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5xvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvu OCA], [https://pdbe.org/5xvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xvu RCSB], [https://www.ebi.ac.uk/pdbsum/5xvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvu ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8IIR9_PLAF7 Q8IIR9_PLAF7]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: Plaf7]]
+[[Category: El Sahili A]]
-[[Category: Lescar, J]]
+[[Category: Lescar J]]
-[[Category: Lin, J Q]]
+[[Category: Lin JQ]]
-[[Category: Ruiz-Carrillo, D]]
+[[Category: Ruiz-Carrillo D]]
-[[Category: Sahili, A El]]
-[[Category: Casein kinase 2 plasmodium falciparum kinase]]
-[[Category: Transferase]]

5xvu: Difference between revisions

Latest revision as of 08:15, 22 November 2023

Crystal structure of the protein kinase CK2 catalytic domain from Plasmodium falciparum bound to ATP

Structural highlights

Function

Publication Abstract from PubMed

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References

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