5dg6
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5dg6 is ON HOLD Authors: Lovell, Scott, Battaile, Kevin P., Mehzabeen, Nurjahan, Damalanka, Vishnu C., Kim, Yunjeong, Alliston, Kevin R., Weerawarna...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==2.35A resolution structure of Norovirus 3CL protease in complex an oxadiazole-based, cell permeable macrocyclic (21-mer) inhibitor== | |
| + | <StructureSection load='5dg6' size='340' side='right'caption='[[5dg6]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5dg6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Norovirus_Hu/1968/US Norovirus Hu/1968/US]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DG6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V66:TERT-BUTYL+[(4S,7S,10S)-7-(CYCLOHEXYLMETHYL)-10-(HYDROXYMETHYL)-5,8,13-TRIOXO-23-OXA-6,9,14,21,22-PENTAAZABICYCLO[18.2.1]TRICOSA-1(22),20-DIEN-4-YL]CARBAMATE'>V66</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dg6 OCA], [https://pdbe.org/5dg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dg6 RCSB], [https://www.ebi.ac.uk/pdbsum/5dg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dg6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://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 == | ||
| + | Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease. | ||
| - | + | Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.,Damalanka VC, Kim Y, Alliston KR, Weerawarna PM, Galasiti Kankanamalage AC, Lushington GH, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC J Med Chem. 2016 Feb 8. PMID:26823007<ref>PMID:26823007</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5dg6" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Chang | + | ==See Also== |
| - | [[Category: | + | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: Kim | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Norovirus Hu/1968/US]] | ||
| + | [[Category: Alliston KR]] | ||
| + | [[Category: Battaile KP]] | ||
| + | [[Category: Chang K-O]] | ||
| + | [[Category: Damalanka VC]] | ||
| + | [[Category: Groutas WC]] | ||
| + | [[Category: Kankanamalage ACG]] | ||
| + | [[Category: Kim Y]] | ||
| + | [[Category: Lovell S]] | ||
| + | [[Category: Lushington GH]] | ||
| + | [[Category: Mehzabeen N]] | ||
| + | [[Category: Weerawarna PM]] | ||
Current revision
2.35A resolution structure of Norovirus 3CL protease in complex an oxadiazole-based, cell permeable macrocyclic (21-mer) inhibitor
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