4xbd: Difference between revisions

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-'''Unreleased structure'''
-The entry 4xbd is ON HOLD
+==1.45A resolution structure of Norovirus 3CL protease complex with a covalently bound dipeptidyl inhibitor (1R,2S)-2-({N-[(benzyloxy)carbonyl]-3-cyclohexyl-L-alanyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (Orthorhombic P Form)==
+<StructureSection load='4xbd' size='340' side='right'caption='[[4xbd]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4xbd]] 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=4XBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XBD FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M40:(1R,2S)-2-({N-[(BENZYLOXY)CARBONYL]-3-CYCLOHEXYL-L-ALANYL}AMINO)-1-HYDROXY-3-[(3S)-2-OXOPYRROLIDIN-3-YL]PROPANE-1-SULFONIC+ACID'>M40</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=4xbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xbd OCA], [https://pdbe.org/4xbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xbd RCSB], [https://www.ebi.ac.uk/pdbsum/4xbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xbd 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 ==
+Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of antinorovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.
-Authors: Lovell, S., Battaile, K.P., Mehzabeen, N., Kankanamalage, A.C.G., Kim, Y., Weerawarna, P.M., Uy, Roxanne A.Z., Damalanka, V.C., Mandadapu, S.R., Alliston, K.R., Groutas, W.C., Chang, K.-O.
+Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies.,Galasiti Kankanamalage AC, Kim Y, Weerawarna PM, Uy RA, Damalanka VC, Mandadapu SR, Alliston KR, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC J Med Chem. 2015 Mar 19. PMID:25761614<ref>PMID:25761614</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Alliston, K.R]]
+<div class="pdbe-citations 4xbd" style="background-color:#fffaf0;"></div>
-[[Category: Chang, K.-O]]
-[[Category: Kankanamalage, A.C.G]]
+==See Also==
-[[Category: Mandadapu, S.R]]
+*[[Virus protease 3D structures|Virus protease 3D structures]]
-[[Category: Battaile, K.P]]
+== References ==
-[[Category: Weerawarna, P.M]]
+<references/>
-[[Category: Lovell, S]]
+__TOC__
-[[Category: Damalanka, V.C]]
+</StructureSection>
-[[Category: Groutas, W.C]]
+[[Category: Large Structures]]
-[[Category: Mehzabeen, N]]
+[[Category: Norovirus Hu/1968/US]]
-[[Category: Kim, Y]]
+[[Category: Alliston KR]]
-[[Category: Uy, Roxanne A.Z]]
+[[Category: Battaile KP]]
+[[Category: Chang K-O]]
+[[Category: Damalanka VC]]
+[[Category: Groutas WC]]
+[[Category: Kankanamalage ACG]]
+[[Category: Kim Y]]
+[[Category: Lovell S]]
+[[Category: Mandadapu SR]]
+[[Category: Mehzabeen N]]
+[[Category: Uy RAZ]]
+[[Category: Weerawarna PM]]