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5v24

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'''Unreleased structure'''
 
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The entry 5v24 is ON HOLD
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==Structure-based drug design of novel ASK1 inhibitors using a fully integrated lead optimization strategy==
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<StructureSection load='5v24' size='340' side='right' caption='[[5v24]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5v24]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V24 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8V7:2-[4-(PROPAN-2-YL)-4H-1,2,4-TRIAZOL-3-YL]-N-(PYRIDIN-2-YL)-1,3-THIAZOLE-4-CARBOXAMIDE'>8V7</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v19|5v19]]</td></tr>
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<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>
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<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=5v24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v24 OCA], [http://pdbe.org/5v24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v24 RCSB], [http://www.ebi.ac.uk/pdbsum/5v24 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v24 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/M3K5_HUMAN M3K5_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).<ref>PMID:8940179</ref> <ref>PMID:8974401</ref> <ref>PMID:9564042</ref> <ref>PMID:9774977</ref> <ref>PMID:10411906</ref> <ref>PMID:10849426</ref> <ref>PMID:10688666</ref> <ref>PMID:11689443</ref> <ref>PMID:11029458</ref> <ref>PMID:11154276</ref> <ref>PMID:14749717</ref> <ref>PMID:11920685</ref> <ref>PMID:12697749</ref> <ref>PMID:15023544</ref> <ref>PMID:14688258</ref> <ref>PMID:16129676</ref> <ref>PMID:17220297</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Structure-based drug design is an iterative process that is an established means to accelerate lead optimization, and is most powerful when integrated with information from different sources. Herein is described the use of such methods in conjunction with deconstruction and re-optimization of a diverse series of ASK1 chemotypes along with high-throughput screening that lead to the identification of a novel series of efficient ASK1 inhibitors displaying robust MAP3K pathway inhibition.
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Authors: Dougan, D.R., Lawson, J.D.
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Structure-based drug design of novel ASK1 inhibitors using an integrated lead optimization strategy.,Gibson TS, Johnson B, Fanjul A, Halkowycz P, Dougan DR, Cole D, Swann S Bioorg Med Chem Lett. 2017 Mar 2. pii: S0960-894X(17)30222-6. doi:, 10.1016/j.bmcl.2017.02.079. PMID:28291695<ref>PMID:28291695</ref>
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Description: Structure-based drug design of novel ASK1 inhibitors using a fully integrated lead optimization strategy
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Lawson, J.D]]
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<div class="pdbe-citations 5v24" style="background-color:#fffaf0;"></div>
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[[Category: Dougan, D.R]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Mitogen-activated protein kinase kinase kinase]]
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[[Category: Dougan, D R]]
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[[Category: Lawson, J D]]
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[[Category: Apoptosis]]
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[[Category: Metal-binding]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]

Revision as of 05:03, 12 April 2017

Structure-based drug design of novel ASK1 inhibitors using a fully integrated lead optimization strategy

5v24, resolution 2.50Å

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