2j92

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{{STRUCTURE_2j92| PDB=2j92 | SCENE= }}
{{STRUCTURE_2j92| PDB=2j92 | SCENE= }}
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'''3C PROTEASE FROM TYPE A10(61) FOOT-AND-MOUTH DISEASE VIRUS-CRYSTAL PACKING MUTANT (K51Q)'''
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===3C PROTEASE FROM TYPE A10(61) FOOT-AND-MOUTH DISEASE VIRUS-CRYSTAL PACKING MUTANT (K51Q)===
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==Overview==
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The 3C protease (3C(pro)) from foot-and-mouth disease virus (FMDV), the causative agent of a widespread and economically devastating disease of domestic livestock, is a potential target for antiviral drug design. We have determined the structure of a new crystal form of FMDV 3C(pro), a chymotrypsin-like cysteine protease, which reveals features that are important for catalytic activity. In particular, we show that a surface loop which was disordered in previous structures adopts a beta-ribbon structure that is conformationally similar to equivalent regions on other picornaviral 3C proteases and some serine proteases. This beta-ribbon folds over the peptide binding cleft and clearly contributes to substrate recognition. Replacement of Cys142 at the tip of the beta-ribbon with different amino acids has a significant impact on enzyme activity and shows that higher activity is obtained with more hydrophobic side chains. Comparison of the structure of FMDV 3C(pro) with homologous enzyme-peptide complexes suggests that this correlation arises because the side chain of Cys142 contacts the hydrophobic portions of the P2 and P4 residues in the peptide substrate. Collectively, these findings provide compelling evidence for the role of the beta-ribbon in catalytic activity and provide valuable insights for the design of FMDV 3C(pro) inhibitors.
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{{ABSTRACT_PUBMED_17065215}}
==About this Structure==
==About this Structure==
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[[Category: Rna replication]]
[[Category: Rna replication]]
[[Category: Thiol protease]]
[[Category: Thiol protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:37:12 2008''

Revision as of 20:37, 28 July 2008

Image:2j92.png

Template:STRUCTURE 2j92

3C PROTEASE FROM TYPE A10(61) FOOT-AND-MOUTH DISEASE VIRUS-CRYSTAL PACKING MUTANT (K51Q)

Template:ABSTRACT PUBMED 17065215

About this Structure

2J92 is a Single protein structure of sequence from Viruses. Full crystallographic information is available from OCA.

Reference

Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis., Sweeney TR, Roque-Rosell N, Birtley JR, Leatherbarrow RJ, Curry S, J Virol. 2007 Jan;81(1):115-24. Epub 2006 Oct 25. PMID:17065215

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