8q6h
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 11)== | |
| + | <StructureSection load='8q6h' size='340' side='right'caption='[[8q6h]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8q6h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8Q6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Q6H FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KI7:3-(3-fluorosulfonyloxy-4-methoxy-phenyl)-7-[(4-fluorosulfonyloxyphenyl)methylamino]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine'>KI7</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8q6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8q6h OCA], [https://pdbe.org/8q6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8q6h RCSB], [https://www.ebi.ac.uk/pdbsum/8q6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8q6h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PI4KB_HUMAN PI4KB_HUMAN] Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity).<ref>PMID:9405935</ref> <ref>PMID:10559940</ref> <ref>PMID:12749687</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The synthesis and characterisation of fluorosulfate covalent inhibitors of the lipid kinase PI4KIIIbeta is described. The conserved lysine residue located within the ATP binding site was targeted, and optimised compounds based upon reversible inhibitors with good activity and physicochemical profile showed strong reversible interactions and slow onset times for the covalent inhibition, resulting in an excellent selectivity profile for the lipid kinase target. X-Ray crystallography demonstrated a distal tyrosine residue could also be targeted using a fluorosulfate strategy. Combination of this knowledge showed that a dual covalent inhibitor could be developed which reveals potential in addressing the challenges associated with drug resistant mutations. | ||
| - | + | Covalent targeting of non-cysteine residues in PI4KIIIbeta.,Cosgrove B, Grant EK, Bertrand S, Down KD, Somers DO, P Evans J, Tomkinson NCO, Barker MD RSC Chem Biol. 2023 Oct 17;4(12):1111-1122. doi: 10.1039/d3cb00142c. eCollection , 2023 Nov 29. PMID:38033723<ref>PMID:38033723</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Somers | + | <div class="pdbe-citations 8q6h" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Somers DO]] | ||
Current revision
HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 11)
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