4xbb: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==1.85A resolution structure of Norovirus 3CL protease complex with a covalently bound dipeptidyl inhibitor diethyl [(1R,2S)-2-[(N-{[(3-chlorobenzyl)oxy]carbonyl}-3-cyclohexyl-L-alanyl)amino]-1-hydroxy-3-(2-oxo-2H-pyrrol-3-yl)propyl]phosphonate==
+<StructureSection load='4xbb' size='340' side='right' caption='[[4xbb]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4xbb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XBB FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZR:DIETHYL+[(1R,2S)-2-[(N-{[(3-CHLOROBENZYL)OXY]CARBONYL}-3-CYCLOHEXYL-L-ALANYL)AMINO]-1-HYDROXY-3-(2-OXO-2H-PYRROL-3-YL)PROPYL]PHOSPHONATE'>3ZR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xbc|4xbc]], [[4xbd|4xbd]]</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=4xbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xbb RCSB], [http://www.ebi.ac.uk/pdbsum/4xbb PDBsum]</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 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.
-The entry 4xbb is ON HOLD  until Paper Publication
+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>
-Authors: Lovell, S., Battaile, K.P., Mehzabeen, N., Kankanamalage, A.C.G., Kim, Y., Weerawarna, P.M., Uy, R.A.Z., Damalanka, V.C., Mandadapu, S.R., Alliston, K.R., Groutas, W.C., Chang, K.-O.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
-[[Category: Uy, R.A.Z]]
+__TOC__
-[[Category: Alliston, K.R]]
+</StructureSection>
-[[Category: Chang, K.-O]]
+[[Category: Calicivirin]]
-[[Category: Kankanamalage, A.C.G]]
+[[Category: Alliston, K R]]
-[[Category: Mandadapu, S.R]]
+[[Category: Battaile, K P]]
-[[Category: Battaile, K.P]]
+[[Category: Chang, K O]]
-[[Category: Weerawarna, P.M]]
+[[Category: Damalanka, V C]]
+[[Category: Groutas, W C]]
+[[Category: Kankanamalage, A C.G]]
+[[Category: Kim, Y]]
 [[Category: Lovell, S]]
-[[Category: Damalanka, V.C]]
+[[Category: Mandadapu, S R]]
-[[Category: Groutas, W.C]]
 [[Category: Mehzabeen, N]]
-[[Category: Kim, Y]]
+[[Category: Uy, R A.Z]]
+[[Category: Weerawarna, P M]]
+[[Category: Antiviral inhibitor]]
+[[Category: Dipeptidyl inhibitor]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Norovirus]]
+[[Category: Norwalk virus]]
+[[Category: Protease]]