3mup

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{{STRUCTURE_3mup| PDB=3mup | SCENE= }}
 
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===cIAP1-BIR3 domain in complex with the Smac-mimetic compound Smac037===
 
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{{ABSTRACT_PUBMED_20954235}}
 
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==Function==
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==cIAP1-BIR3 domain in complex with the Smac-mimetic compound Smac037==
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[[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>
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<StructureSection load='3mup' size='340' side='right'caption='[[3mup]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3mup]] is a 4 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=3MUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MUP FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SMK:(3S,6S,7R,9AS)-6-{[(2S)-2-AMINOBUTANOYL]AMINO}-7-(2-AMINOETHYL)-N-(DIPHENYLMETHYL)-5-OXOOCTAHYDRO-1H-PYRROLO[1,2-A]AZEPINE-3-CARBOXAMIDE'>SMK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mup OCA], [https://pdbe.org/3mup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mup RCSB], [https://www.ebi.ac.uk/pdbsum/3mup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mup ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Inhibitor of apoptosis proteins (IAPs) are negative regulators of apoptosis. Since IAPs are overexpressed in many tumors, where they confer chemoresistance, small molecules inactivating IAPs have been proposed as anticancer agents. Accordingly, a number of IAP-binding pro-apoptotic compounds that mimic the sequence corresponding to the N-terminal tetrapeptide of Smac/DIABLO, the natural endogenous IAPs inhibitor, have been developed. Here we report the crystal structures of the BIR3 domain of cIAP1 in complex with Smac037, a Smac-mimetic known to bind potently to the XIAP-BIR3 domain and to induce degradation of cIAP1, and in complex with the novel Smac-mimetic compound Smac066. Thermal stability and fluorescence polarization assays show the stabilizing effect and the high affinity of both Smac037 and Smac066 for cIAP1- and cIAP2-BIR3 domains.
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==About this Structure==
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Recognition of Smac-mimetic compounds by the BIR3 domain of cIAP1.,Cossu F, Malvezzi F, Canevari G, Mastrangelo E, Lecis D, Delia D, Seneci P, Scolastico C, Bolognesi M, Milani M Protein Sci. 2010 Oct 15. PMID:20954235<ref>PMID:20954235</ref>
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[[3mup]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MUP OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:020954235</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 3mup" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Canevari, G.]]
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[[Category: Large Structures]]
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[[Category: Cossu, F.]]
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[[Category: Canevari G]]
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[[Category: Malvezzi, F.]]
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[[Category: Cossu F]]
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[[Category: Milani, M.]]
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[[Category: Malvezzi F]]
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[[Category: Apoptosis inhibitor]]
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[[Category: Milani M]]
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[[Category: Zinc-finger motif]]
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Current revision

cIAP1-BIR3 domain in complex with the Smac-mimetic compound Smac037

PDB ID 3mup

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