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| | <StructureSection load='2iph' size='340' side='right'caption='[[2iph]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='2iph' size='340' side='right'caption='[[2iph]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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://proteopedia.org/fgij/fg.htm?mol=2IPH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2iph]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Southampton_virus_(serotype_3) Southampton virus (serotype 3)]. 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 [https://proteopedia.org/fgij/fg.htm?mol=2IPH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=2iph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iph OCA], [https://pdbe.org/2iph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iph RCSB], [https://www.ebi.ac.uk/pdbsum/2iph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iph ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/POLG_SOUV3 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] | + | [https://www.uniprot.org/uniprot/POLG_SOUV3 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <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> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
| + | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| - | *[[Virus proteases 3D strutures|Virus proteases 3D strutures]] | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hu/nv/shv/1991/uk]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hussey, R J]] | + | [[Category: Hussey RJ]] |
| - | [[Category: Alpha helix]]
| + | |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
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.
See Also
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
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