6juu
From Proteopedia
(Difference between revisions)
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==Crystal structure of ZAK in complex with compound 6r== | ==Crystal structure of ZAK in complex with compound 6r== | ||
| - | <StructureSection load='6juu' size='340' side='right'caption='[[6juu]]' scene=''> | + | <StructureSection load='6juu' size='340' side='right'caption='[[6juu]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6JUU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6juu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6JUU FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6juu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6juu OCA], [http://pdbe.org/6juu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6juu RCSB], [http://www.ebi.ac.uk/pdbsum/6juu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6juu ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C9R:~{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]naphthalene-1-sulfonamide'>C9R</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ZAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://proteopedia.org/fgij/fg.htm?mol=6juu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6juu OCA], [http://pdbe.org/6juu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6juu RCSB], [http://www.ebi.ac.uk/pdbsum/6juu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6juu ProSAT]</span></td></tr> | ||
</table> | </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> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6juu" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Mitogen-activated protein kinase kinase kinase|Mitogen-activated protein kinase kinase kinase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Kong | + | [[Category: Mitogen-activated protein kinase kinase kinase]] |
| - | [[Category: Yun | + | [[Category: Kong, L L]] |
| + | [[Category: Yun, C H]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Structural protein]] | ||
| + | [[Category: Zak]] | ||
Revision as of 07:29, 4 November 2020
Crystal structure of ZAK in complex with compound 6r
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