This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6jut
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of ZAK in complex with compound 6k== | |
| + | <StructureSection load='6jut' size='340' side='right'caption='[[6jut]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6jut]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JUT FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C9O:~{N}-[2,4-bis(fluoranyl)-3-[4-(3-methoxy-1~{H}-pyrazolo[3,4-b]pyridin-5-yl)-1,2,3-triazol-1-yl]phenyl]-3-bromanyl-benzenesulfonamide'>C9O</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jut OCA], [http://pdbe.org/6jut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jut RCSB], [http://www.ebi.ac.uk/pdbsum/6jut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jut ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MLTK_HUMAN MLTK_HUMAN]] Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'.<ref>PMID:10924358</ref> <ref>PMID:11042189</ref> <ref>PMID:11836244</ref> <ref>PMID:15172994</ref> <ref>PMID:15342622</ref> <ref>PMID:15684425</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, 6p binds tightly to ZAK protein ( Kd = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC50 = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound 6p may serve as a lead compound for new anti-HCM drug discovery. | ||
| - | + | Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.,Yang J, Shibu MA, Kong L, Luo J, BadrealamKhan F, Huang Y, Tu ZC, Yun CH, Huang CY, Ding K, Lu X J Med Chem. 2019 Jun 17. doi: 10.1021/acs.jmedchem.9b00664. PMID:31244114<ref>PMID:31244114</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Kong, L | + | <div class="pdbe-citations 6jut" style="background-color:#fffaf0;"></div> |
| - | [[Category: Yun, C | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mitogen-activated protein kinase kinase kinase]] | ||
| + | [[Category: Kong, L L]] | ||
| + | [[Category: Yun, C H]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Structural protein]] | ||
| + | [[Category: Zak]] | ||
Revision as of 06:13, 24 July 2019
Crystal structure of ZAK in complex with compound 6k
| |||||||||||
