6y6f: Difference between revisions
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<StructureSection load='6y6f' size='340' side='right'caption='[[6y6f]], [[Resolution|resolution]] 1.98Å' scene=''> | <StructureSection load='6y6f' size='340' side='right'caption='[[6y6f]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6y6f]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6y6f]] 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=6Y6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y6F FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98Å</td></tr> | ||
<tr id=' | <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=OD2:2-[6-(4-methylsulfanylphenyl)thieno[3,2-d]pyrimidin-4-yl]sulfanylethanoic+acid'>OD2</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=6y6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y6f OCA], [https://pdbe.org/6y6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y6f RCSB], [https://www.ebi.ac.uk/pdbsum/6y6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y6f ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ST17B_HUMAN ST17B_HUMAN] Phosphorylates myosin light chains (By similarity). Acts as a positive regulator of apoptosis.<ref>PMID:9786912</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arrowsmith CH]] | |||
[[Category: Arrowsmith | [[Category: Bountra C]] | ||
[[Category: Bountra | [[Category: Chaikuad A]] | ||
[[Category: Chaikuad | [[Category: Drewry D]] | ||
[[Category: Drewry | [[Category: Edwards AM]] | ||
[[Category: Edwards | [[Category: Knapp S]] | ||
[[Category: Knapp | |||
Latest revision as of 16:20, 24 January 2024
Crystal structure of STK17B (DRAK2) in complex with PKIS43Crystal structure of STK17B (DRAK2) in complex with PKIS43
Structural highlights
FunctionST17B_HUMAN Phosphorylates myosin light chains (By similarity). Acts as a positive regulator of apoptosis.[1] Publication Abstract from PubMedSTK17B is a member of the death-associated protein kinase family and has been genetically linked to the development of diverse diseases. However, the role of STK17B in normal and disease pathology is poorly defined. Here, we present the discovery of thieno[3,2-d] pyrimidine SGC-STK17B-1 (11s), a high-quality chemical probe for this understudied "dark" kinase. 11s is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallography of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor. Molecular dynamic simulations of STK17B revealed the flexibility of the P-loop and a wide range of R41 conformations available to the apo-protein. The isomeric thieno[2,3-d]pyrimidine SGC-STK17B-1N (19g) was identified as a negative control compound. The >100-fold lower activity of 19g on STK17B was attributed to the reduced basicity of its pyrimidine N1. A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation.,Picado A, Chaikuad A, Wells CI, Shrestha S, Zuercher WJ, Pickett JE, Kwarcinski FE, Sinha P, de Silva CS, Zutshi R, Liu S, Kannan N, Knapp S, Drewry DH, Willson TM J Med Chem. 2020 Dec 10;63(23):14626-14646. doi: 10.1021/acs.jmedchem.0c01174., Epub 2020 Nov 20. PMID:33215924[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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