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| | <StructureSection load='2q6f' size='340' side='right'caption='[[2q6f]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2q6f' size='340' side='right'caption='[[2q6f]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2q6f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Avian_infectious_bronchitis_virus Avian infectious bronchitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q6F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2q6f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Infectious_bronchitis_virus Infectious bronchitis virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q6F FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=010:PHENYLMETHANOL'>010</scene>, <scene name='pdbligand=02J:5-METHYL-1,2-OXAZOLE-3-CARBOXYLIC+ACID'>02J</scene>, <scene name='pdbligand=PJE:(E,4S)-4-AZANYL-5-[(3S)-2-OXIDANYLIDENEPYRROLIDIN-3-YL]PENT-2-ENOIC+ACID'>PJE</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q6d|2q6d]], [[2q6g|2q6g]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=010:PHENYLMETHANOL'>010</scene>, <scene name='pdbligand=02J:5-METHYL-1,2-OXAZOLE-3-CARBOXYLIC+ACID'>02J</scene>, <scene name='pdbligand=PJE:(E,4S)-4-AZANYL-5-[(3S)-2-OXIDANYLIDENEPYRROLIDIN-3-YL]PENT-2-ENOIC+ACID'>PJE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">M41 3C-like protease gene ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11120 Avian infectious bronchitis virus])</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=2q6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6f OCA], [https://pdbe.org/2q6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q6f RCSB], [https://www.ebi.ac.uk/pdbsum/2q6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6f ProSAT]</span></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=2q6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6f OCA], [https://pdbe.org/2q6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q6f RCSB], [https://www.ebi.ac.uk/pdbsum/2q6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/R1A_IBVM R1A_IBVM] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. Activity of PL-PRO is dependent on zinc (By similarity). The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). The peptide p16 might be involved in the EGF signaling pathway (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Avian infectious bronchitis virus]] | + | [[Category: Infectious bronchitis virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bartlam, M]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Rao, Z H]] | + | [[Category: Bartlam M]] |
| - | [[Category: Xue, F]] | + | [[Category: Rao ZH]] |
| - | [[Category: Xue, X Y]] | + | [[Category: Xue F]] |
| - | [[Category: Yang, H T]] | + | [[Category: Xue XY]] |
| - | [[Category: 3c-like proteinase]] | + | [[Category: Yang HT]] |
| - | [[Category: Coronavirus]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Ibv]]
| + | |
| - | [[Category: Main protease]]
| + | |
| - | [[Category: Michael acceptor inhibitor]]
| + | |
| Structural highlights
Function
R1A_IBVM The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. Activity of PL-PRO is dependent on zinc (By similarity). The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1-phosphate (ADRP)-binding function (By similarity). The peptide p16 might be involved in the EGF signaling pathway (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity).
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
Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) M(pro) and a severe acute respiratory syndrome CoV (SARS-CoV) M(pro) mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M(pro). A monomeric form of IBV M(pro) was identified for the first time in CoV M(pro) structures. A comparison of these two structures to other available M(pro) structures provides new insights for the design of substrate-based inhibitors targeting CoV M(pro)s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M(pro) and was found to demonstrate in vitro inactivation of IBV M(pro) and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M(pro).
Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design.,Xue X, Yu H, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC, Liao M, Bartlam M, Rao Z J Virol. 2008 Mar;82(5):2515-27. Epub 2007 Dec 19. PMID:18094151[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xue X, Yu H, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC, Liao M, Bartlam M, Rao Z. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. J Virol. 2008 Mar;82(5):2515-27. Epub 2007 Dec 19. PMID:18094151 doi:10.1128/JVI.02114-07
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