View source for 5e0j


==1.20 A resolution structure of Norovirus 3CL protease in complex with a triazole-based macrocyclic (21-mer) inhibitor==
<StructureSection load='5e0j' size='340' side='right'caption='[[5e0j]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5e0j]] is a 1 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=5E0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E0J 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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5LJ:(PHENYLMETHYL)+~{N}-[(12~{S},15~{S},18~{S})-15-(CYCLOHEXYLMETHYL)-12-(HYDROXYMETHYL)-9,14,17-TRIS(OXIDANYLIDENE)-1,8,13,16,21,22-HEXAZABICYCLO[18.2.1]TRICOSA-20(23),21-DIEN-18-YL]CARBAMATE'>5LJ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5e0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0j OCA], [https://pdbe.org/5e0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e0j RCSB], [https://www.ebi.ac.uk/pdbsum/5e0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0j 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 ==
Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.

Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies.,Weerawarna PM, Kim Y, Galasiti Kankanamalage AC, Damalanka VC, Lushington GH, Alliston KR, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC Eur J Med Chem. 2016 Aug 25;119:300-18. doi: 10.1016/j.ejmech.2016.04.013. Epub, 2016 Apr 25. PMID:27235842<ref>PMID:27235842</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5e0j" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<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]]