1g0v
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THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT, MVV
OverviewOverview
The yeast IA3 polypeptide consists of only 68 residues, and the free, inhibitor has little intrinsic secondary structure. IA3 showed, subnanomolar potency toward its target, proteinase A from Saccharomyces, cerevisiae, and did not inhibit any of a large number of aspartic, proteinases with similar sequences/structures from a wide variety of other, species. Systematic truncation and mutagenesis of the IA3 polypeptide, revealed that the inhibitory activity is located in the N-terminal half of, the sequence. Crystal structures of different forms of IA3 complexed with, proteinase A showed that residues in the N-terminal half of the IA3, sequence became ordered and formed an almost perfect alpha-helix in the, active site of the enzyme. This potent, specific interaction was directed, primarily by hydrophobic interactions made by three key features in the, inhibitory sequence. Whereas IA3 was cut as a substrate by the nontarget, aspartic proteinases, it was not cleaved by proteinase A. The random coil, IA3 polypeptide escapes cleavage by being stabilized in a helical, conformation upon interaction with the active site of proteinase A. This, results, paradoxically, in potent selective inhibition of the target, enzyme.
About this StructureAbout this Structure
1G0V is a Protein complex structure of sequences from Saccharomyces cerevisiae with MAN and NAG as ligands. Active as Saccharopepsin, with EC number 3.4.23.25 Full crystallographic information is available from OCA.
ReferenceReference
The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae., Phylip LH, Lees WE, Brownsey BG, Bur D, Dunn BM, Winther JR, Gustchina A, Li M, Copeland T, Wlodawer A, Kay J, J Biol Chem. 2001 Jan 19;276(3):2023-30. Epub 2000 Oct 19. PMID:11042188
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