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5m6n
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Small Molecule inhibitors of IAP== | |
| + | <StructureSection load='5m6n' size='340' side='right' caption='[[5m6n]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5m6n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M6N FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7H9:1-[6-[(4-FLUOROPHENYL)METHYL]-3,3-DIMETHYL-2~{H}-PYRROLO[3,2-B]PYRIDIN-1-YL]-2-[(2~{R},5~{R})-5-METHYL-2-[[(3~{R})-3-METHYLMORPHOLIN-4-YL]METHYL]PIPERAZIN-4-IUM-1-YL]ETHANONE'>7H9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5m6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m6n OCA], [http://pdbe.org/5m6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m6n RCSB], [http://www.ebi.ac.uk/pdbsum/5m6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m6n ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/BIRC2_HUMAN BIRC2_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.<ref>PMID:15665297</ref> <ref>PMID:18082613</ref> <ref>PMID:21145488</ref> <ref>PMID:21653699</ref> <ref>PMID:21931591</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Overexpression of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies and NMR solution conformational analysis was successfully applied to a fragment-derived lead resulting in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for IAP biology. | ||
| - | + | Discovery of a Potent Non-peptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-linked Inhibitor of Apoptosis Protein (XIAP).,Tamanini E, Buck IM, Chessari G, Chiarparin E, Day JEH, Frederickson M, Griffiths-Jones CM, Hearn K, Heightman TD, Iqbal A, Johnson CN, Lewis EJ, Martins V, Peakman T, Reader M, Rich SJ, Ward GA, Williams PA, Wilsher NE J Med Chem. 2017 May 11. doi: 10.1021/acs.jmedchem.6b01877. PMID:28492317<ref>PMID:28492317</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5m6n" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Williams, P A]] | ||
| + | [[Category: Apoptosis]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Metal-binding]] | ||
| + | [[Category: Xiap]] | ||
| + | [[Category: Xiap#1]] | ||
Revision as of 13:36, 24 May 2017
Small Molecule inhibitors of IAP
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