2q6g
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= rep ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus]) | |GENE= rep ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus]) | ||
| + | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05409 Peptidase_C30]</span> | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6g OCA], [http://www.ebi.ac.uk/pdbsum/2q6g PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=2q6g RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 29: | ||
[[Category: Xue, X Y.]] | [[Category: Xue, X Y.]] | ||
[[Category: Yang, H T.]] | [[Category: Yang, H T.]] | ||
| - | [[Category: | + | [[Category: 3c-like proteinase;substrate]] |
| + | [[Category: coronavirus]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| + | [[Category: main protease]] | ||
| + | [[Category: sars-cov]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 10:02:34 2008'' |
Revision as of 08:02, 26 March 2008
| |||||||
| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | rep (SARS coronavirus) | ||||||
| Domains: | Peptidase_C30 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of SARS-CoV main protease H41A mutant in complex with an N-terminal substrate
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
2Q6G is a Single protein structure of sequence from Sars coronavirus. 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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