3q3y: Difference between revisions
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==Complex structure of HEVB EV93 main protease 3C with Compound 1 (AG7404)== | ==Complex structure of HEVB EV93 main protease 3C with Compound 1 (AG7404)== | ||
<StructureSection load='3q3y' size='340' side='right' caption='[[3q3y]], [[Resolution|resolution]] 1.32Å' scene=''> | <StructureSection load='3q3y' size='340' side='right' caption='[[3q3y]], [[Resolution|resolution]] 1.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3q3y]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3q3y]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Enterovirus_b Enterovirus b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q3Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q3Y FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=PI:HYDROGENPHOSPHATE+ION'>PI</scene>, <scene name='pdbligand=XNV:ETHYL+(4R)-4-({(2S)-2-[3-{[(5-METHYL-1,2-OXAZOL-3-YL)CARBONYL]AMINO}-2-OXOPYRIDIN-1(2H)-YL]PENT-4-YNOYL}AMINO)-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>XNV</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=PI:HYDROGENPHOSPHATE+ION'>PI</scene>, <scene name='pdbligand=XNV:ETHYL+(4R)-4-({(2S)-2-[3-{[(5-METHYL-1,2-OXAZOL-3-YL)CARBONYL]AMINO}-2-OXOPYRIDIN-1(2H)-YL]PENT-4-YNOYL}AMINO)-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>XNV</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q3x|3q3x]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q3x|3q3x]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=138949 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=138949 Enterovirus B])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></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=3q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q3y RCSB], [http://www.ebi.ac.uk/pdbsum/3q3y PDBsum]</span></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=3q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3y OCA], [http://pdbe.org/3q3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q3y RCSB], [http://www.ebi.ac.uk/pdbsum/3q3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q3y ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3q3y" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[3C protease|3C protease]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Enterovirus b]] | ||
[[Category: Picornain 3C]] | [[Category: Picornain 3C]] | ||
[[Category: Arnan, C]] | [[Category: Arnan, C]] | ||
Revision as of 01:43, 5 August 2016
Complex structure of HEVB EV93 main protease 3C with Compound 1 (AG7404)Complex structure of HEVB EV93 main protease 3C with Compound 1 (AG7404)
Structural highlights
Publication Abstract from PubMedThe Enteroviruses genus of the Picornaviridae family is abundant with common human pathogens that belong to rhinoviruses (HRVs) and enteroviruses (EVs), including diverse echo-, coxsackie- and polio- viruses. They cause a wide spectrum of clinical manifestations ranging from asymptomatic to severe diseases with neurological and/or cardiac manifestations. Pandemic outbreaks of EVs may be accompanied with meningitis and/or paralysis and can be fatal. However, there is no effective prophylaxis or antiviral treatment available against most EVs. The EV RNA genome directs the synthesis of a single polyprotein that is auto-catalytically processed into mature proteins by the 3C protease at Gln downward arrowGly sites, with narrow conserved substrate specificity. These cleavages are essential for virus replication, making 3C(pro) an excellent target for antivirus drug development. In this study, we report the first crystal structures of the 3C(pro) from an enterovirus B, EV-93, a recently identified pathogen, alone and in complex with the anti-HRV molecules Compound 1 (AG7404) and Rupintrivir (AG7088), at 1.9, 1.3 and 1.5-A resolution, respectively. The EV-93 3C(pro) adopts a chymotrypsin-like fold with a canonically configured oxyanion hole and a substrate binding pocket similar to that of rhino-, coxsackie- and poliovirus 3C proteases. We show that Compound 1 and Rupintrivir are both active against EV-93 in infected cells, and inhibit the proteolytic activity of EV-93 3C(pro) in vitro. These results provide a framework for further structure-guided optimization of the tested compounds to produce antiviral drugs against a broad range of EV species. Structural basis for antiviral inhibition of the main protease 3C from human enterovirus 93.,Costenaro L, Kaczmarska Z, Arnan C, Janowski R, Coutard B, Sola M, Gorbalenya AE, Norder H, Canard B, Coll M J Virol. 2011 Aug 10. PMID:21835784[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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