2j92
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3C PROTEASE FROM TYPE A10(61) FOOT-AND-MOUTH DISEASE VIRUS-CRYSTAL PACKING MUTANT (K51Q)
OverviewOverview
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.
About this StructureAbout this Structure
2J92 is a Single protein structure of sequence from Foot-and-mouth disease virus (strain a10-61). Active as Picornain 3C, with EC number 3.4.22.28 Full crystallographic information is available from OCA.
ReferenceReference
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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