5tg1
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==1.40 A resolution structure of Norovirus 3CL protease in complex with the a m-chlorophenyl substituted macrocyclic inhibitor (17-mer)== | |
| + | <StructureSection load='5tg1' size='340' side='right' caption='[[5tg1]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5tg1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TG1 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V56:(4S,7S,17S)-17-(3-CHLOROPHENYL)-7-(HYDROXYMETHYL)-4-(2-METHYLPROPYL)-1-OXA-3,6,11-TRIAZACYCLOHEPTADECANE-2,5,10-TRIONE'>V56</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tg2|5tg2]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calicivirin Calicivirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.66 3.4.22.66] </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=5tg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tg1 OCA], [http://pdbe.org/5tg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tg1 RCSB], [http://www.ebi.ac.uk/pdbsum/5tg1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tg1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/POLG_NVN68 POLG_NVN68]] Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Protein P22 may play a role in targeting replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref> RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. This report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein. | ||
| - | + | Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease.,Damalanka VC, Kim Y, Galasiti Kankanamalage AC, Lushington GH, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC Eur J Med Chem. 2016 Dec 21;127:41-61. doi: 10.1016/j.ejmech.2016.12.033. PMID:28038326<ref>PMID:28038326</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Chang, K | + | <div class="pdbe-citations 5tg1" style="background-color:#fffaf0;"></div> |
| - | [[Category: Kankanamalage, A | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Calicivirin]] | ||
| + | [[Category: Battaile, K P]] | ||
| + | [[Category: Chang, K O]] | ||
| + | [[Category: Damalanka, V C]] | ||
| + | [[Category: Groutas, W C]] | ||
| + | [[Category: Kankanamalage, A C.G]] | ||
| + | [[Category: Kim, Y]] | ||
[[Category: Lovell, S]] | [[Category: Lovell, S]] | ||
| - | [[Category: Damalanka, V.C]] | ||
| - | [[Category: Groutas, W.C]] | ||
[[Category: Mehzabeen, N]] | [[Category: Mehzabeen, N]] | ||
| - | [[Category: | + | [[Category: Antiviral inhibitor]] |
| + | [[Category: Macrocyclic inhibitor]] | ||
| + | [[Category: Norovirus]] | ||
| + | [[Category: Norwalk virus]] | ||
| + | [[Category: Protease]] | ||
| + | [[Category: Protease-protease inhibitor complex]] | ||
Revision as of 16:38, 18 January 2017
1.40 A resolution structure of Norovirus 3CL protease in complex with the a m-chlorophenyl substituted macrocyclic inhibitor (17-mer)
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