3rc5

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{{STRUCTURE_3rc5| PDB=3rc5 | SCENE= }}
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==Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease==
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===Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease===
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<StructureSection load='3rc5' size='340' side='right' caption='[[3rc5]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21507982}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3rc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RC5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RC5 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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rc6|3rc6]], [[3rc4|3rc4]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</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=3rc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rc5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rc5 RCSB], [http://www.ebi.ac.uk/pdbsum/3rc5 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hepatitis C NS3/4A protease is a prime therapeutic target responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A and 5A5B, and two host-cell adapter proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host-cell cleavage sites are determined and compared to the crystal structures of viral substrates. Two distinct protease conformations are observed and correlate with substrate specificity: (1) 3-4A, 4A4B, 5A5B and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease and (2) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.
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==Function==
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Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease.,Romano KP, Laine JM, Deveau LM, Cao H, Massi F, Schiffer CA J Virol. 2011 Apr 20. PMID:21507982<ref>PMID:21507982</ref>
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[[http://www.uniprot.org/uniprot/MAVS_HUMAN MAVS_HUMAN]] Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.<ref>PMID:16125763</ref> <ref>PMID:16153868</ref> <ref>PMID:16177806</ref> <ref>PMID:16127453</ref> <ref>PMID:19631370</ref> <ref>PMID:20451243</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3rc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RC5 OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021507982</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Hepatitis c virus subtype 1a]]
[[Category: Hepatitis c virus subtype 1a]]
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[[Category: Romano, K P.]]
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[[Category: Romano, K P]]
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[[Category: Schiffer, C A.]]
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[[Category: Schiffer, C A]]
[[Category: Drug design]]
[[Category: Drug design]]
[[Category: Drug resistance]]
[[Category: Drug resistance]]

Revision as of 11:10, 19 December 2014

Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease

3rc5, resolution 1.60Å

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