5wej
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5wej is ON HOLD until Paper Publication Authors: Lovell, S., Battaile, K.P., Mehzabeen, N., Damalanka, V.C., Kim, Y., Kankanamalage, A.C.G., Rathnay...) |
|||
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==1.95 A resolution structure of Norovirus 3CL protease in complex with a dipeptidyl oxazolidinone-based inhibitor== | |
| + | <StructureSection load='5wej' size='340' side='right'caption='[[5wej]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5wej]] 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=5WEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WEJ 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]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V45:(2S)-2-{(5S)-5-[(3-chlorophenyl)methyl]-2-oxo-1,3-oxazolidin-3-yl}-4-methyl-N-{(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}pentanamide'>V45</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=5wej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wej OCA], [https://pdbe.org/5wej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wej RCSB], [https://www.ebi.ac.uk/pdbsum/5wej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wej 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 == | ||
| + | Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display anti-norovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography. | ||
| - | + | Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.,Damalanka VC, Kim Y, Galasiti Kankanamalage AC, Rathnayake AD, Mehzabeen N, Battaile KP, Lovell S, Nguyen HN, Lushington GH, Chang KO, Groutas WC Eur J Med Chem. 2018 Jan 1;143:881-890. doi: 10.1016/j.ejmech.2017.12.014. Epub, 2017 Dec 6. PMID:29227928<ref>PMID:29227928</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5wej" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Battaile | + | ==See Also== |
| - | [[Category: | + | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| - | [[Category: Damalanka | + | == References == |
| - | [[Category: Groutas | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Rathnayake | + | [[Category: Norovirus Hu/1968/US]] |
| + | [[Category: Battaile KP]] | ||
| + | [[Category: Chang KO]] | ||
| + | [[Category: Damalanka VC]] | ||
| + | [[Category: Groutas WC]] | ||
| + | [[Category: Kankanamalage ACG]] | ||
| + | [[Category: Kim Y]] | ||
| + | [[Category: Lovell S]] | ||
| + | [[Category: Mehzabeen N]] | ||
| + | [[Category: Nguyen HN]] | ||
| + | [[Category: Rathnayake AD]] | ||
Current revision
1.95 A resolution structure of Norovirus 3CL protease in complex with a dipeptidyl oxazolidinone-based inhibitor
| |||||||||||
