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2iph

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Revision as of 08:40, 4 July 2018

X-ray Structure at 1.75 A Resolution of a Norovirus Protease Linked to an Active Site Directed Peptide Inhibitor

Structural highlights

2iph is a 2 chain structure with sequence from Hu/nv/shv/1991/uk. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLG_SOUV3] 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 (By similarity). NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity (By similarity). Protein P22 may play a role in targeting replication complex to intracellular membranes. 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 (By similarity). 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave polyadenylate-binding protein thereby inhibiting cellular translation.[PROSITE-ProRule:PRU00870] 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 codes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).[PROSITE-ProRule:PRU00539]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Noroviruses are the major cause of human epidemic nonbacterial gastroenteritis. Viral replication requires a 3C cysteine protease that cleaves a 200 kDa viral polyprotein into its constituent functional proteins. Here we describe the X-ray structure of the Southampton norovirus 3C protease (SV3CP) bound to an active site-directed peptide inhibitor (MAPI) which has been refined at 1.7 A resolution. The inhibitor, acetyl-Glu-Phe-Gln-Leu-Gln-X, which is based on the most rapidly cleaved recognition sequence in the 200 kDa polyprotein substrate, reacts covalently through its propenyl ethyl ester group (X) with the active site nucleophile, Cys 139. The structure permits, for the first time, the identification of substrate recognition and binding groups in a noroviral 3C protease and thus provides important new information for the development of antiviral prophylactics.

A Structural Study of Norovirus 3C Protease Specificity: Binding of a Designed Active Site-Directed Peptide Inhibitor.,Hussey RJ, Coates L, Gill RS, Erskine PT, Coker SF, Mitchell E, Cooper JB, Wood S, Broadbridge R, Clarke IN, Lambden PR, Shoolingin-Jordan PM Biochemistry. 2010 Dec 15. PMID:21128685^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hussey RJ, Coates L, Gill RS, Erskine PT, Coker SF, Mitchell E, Cooper JB, Wood S, Broadbridge R, Clarke IN, Lambden PR, Shoolingin-Jordan PM. A Structural Study of Norovirus 3C Protease Specificity: Binding of a Designed Active Site-Directed Peptide Inhibitor. Biochemistry. 2010 Dec 15. PMID:21128685 doi:10.1021/bi1008497

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2iph"

Categories: Hu/nv/shv/1991/uk | Hussey, R J | Alpha helix | Beta barrel | Hydrolase-hydrolase inhibitor complex

@@ Line 1: / Line 1: @@
 ==X-ray Structure at 1.75 A Resolution of a Norovirus Protease Linked to an Active Site Directed Peptide Inhibitor==
 <StructureSection load='2iph' size='340' side='right' caption='[[2iph]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2iph]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hu/nv/shv/1991/uk Hu/nv/shv/1991/uk]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IPH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LGG:N-ACETYL-L-ALPHA-GLUTAMYL-L-PHENYLALANYL-L-GLUTAMINYL-N-[(1S)-4-AMINO-1-(2-CARBOXYETHYL)-4-OXOBUTYL]-L-LEUCINAMIDE'>LGG</scene></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=2iph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iph OCA], [http://pdbe.org/2iph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2iph RCSB], [http://www.ebi.ac.uk/pdbsum/2iph PDBsum]</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=2iph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iph OCA], [http://pdbe.org/2iph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2iph RCSB], [http://www.ebi.ac.uk/pdbsum/2iph PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2iph ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ip/2iph_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ip/2iph_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2iph ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 31: @@
 ==See Also==
 *[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
+*[[3C protease|3C protease]]
 == References ==
 <references/>

2iph

From Proteopedia

Revision as of 08:40, 4 July 2018

X-ray Structure at 1.75 A Resolution of a Norovirus Protease Linked to an Active Site Directed Peptide Inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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