2q6f
From Proteopedia
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| - | [[Image:2q6f.jpg|left|200px]] | + | [[Image:2q6f.jpg|left|200px]] |
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| - | '''Crystal structure of infectious bronchitis virus (IBV) main protease in complex with a Michael acceptor inhibitor N3''' | + | {{Structure |
| + | |PDB= 2q6f |SIZE=350|CAPTION= <scene name='initialview01'>2q6f</scene>, resolution 2.0Å | ||
| + | |SITE= <scene name='pdbsite=AC1:3ih+Binding+Site+For+Residue+A+1145'>AC1</scene> and <scene name='pdbsite=AC2:3ih+Binding+Site+For+Residue+B+1146'>AC2</scene> | ||
| + | |LIGAND= <scene name='pdbligand=3IH:N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N~1~-((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE'>3IH</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= M41 3C-like protease gene ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11120 Infectious bronchitis virus]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of infectious bronchitis virus (IBV) main protease in complex with a Michael acceptor inhibitor N3''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2Q6F is a [ | + | 2Q6F is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Infectious_bronchitis_virus Infectious bronchitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6F OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/18094151 18094151] |
[[Category: Infectious bronchitis virus]] | [[Category: Infectious bronchitis virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:22:18 2008'' |
Revision as of 16:22, 20 March 2008
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| , resolution 2.0Å | |||||||
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| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | M41 3C-like protease gene (Infectious bronchitis virus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of infectious bronchitis virus (IBV) main protease in complex with a Michael acceptor inhibitor N3
Overview
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).
About this Structure
2Q6F is a Single protein structure of sequence from Infectious bronchitis virus. Full crystallographic information is available from OCA.
Reference
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
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