Abstract
A synthetic cyclic peptide, reported to be a tight-binding inhibitor of serine proteases, is instead found to be a good substrate, as is the linear peptide of the same sequence. Both of the peptides, designed to mimic the binding loop of chymotrypsin inhibitor 2 (CI2), were cleaved by subtilisin primarily at the CI2 reactive site Met-59-Glu-60 bond, revealing that the sequence, in the absence of the structural context of the inhibitor, provides sufficient specificity for hydrolysis of this bond. Insights from the crystal structure of the CI2/subtilisin complex, together with biochemical analysis of a CI2 Gly-83 deletion mutant, have allowed us to identify key features that make CI2 an effective inhibitor, while the cyclic and linear peptides are substrates.
Original language | English (US) |
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Pages (from-to) | 6484-6492 |
Number of pages | 9 |
Journal | Biochemistry |
Volume | 42 |
Issue number | 21 |
DOIs | |
State | Published - Jun 3 2003 |
ASJC Scopus subject areas
- Biochemistry