2q6d: Difference between revisions

Revision as of 14:26, 4 May 2008

Crystal structure of infectious bronchitis virus (IBV) main protease

OverviewOverview

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 StructureAbout this Structure

2Q6D is a Single protein structure of sequence from Infectious bronchitis virus. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 14:25:58 2008

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OCA

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 [[Image:2q6d.jpg|left|200px]]
- {{Structure
+<!--
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-|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])
+-->
-|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05409 Peptidase_C30]</span>
+{{STRUCTURE_2q6d|  PDB=2q6d  |  SCENE=  }}
-|RELATEDENTRY=[[2q6f|2Q6F]], [[2q6g|2Q6G]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6d OCA], [http://www.ebi.ac.uk/pdbsum/2q6d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q6d RCSB]</span>
-}}
 '''Crystal structure of infectious bronchitis virus (IBV) main protease'''
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 [[Category: Yang, H T.]]
 [[Category: 3c-like proteinase]]
-[[Category: coronavirus]]
+[[Category: Coronavirus]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: ibv]]
+[[Category: Ibv]]
-[[Category: main protease]]
+[[Category: Main protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:25:58 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:45:23 2008''