Abstract
Despite the importance of limited proteolysis in biological systems it is often difficult to rationalize why a proteinase hydrolyses a particular bond, given a simple sequence specificity alone. Understanding of the structural properties limiting the proteolysis represents a first step on the pathway to control and manipulation of this phenomena. An expanded set of nick-sites in proteins of known tertiary structure, cut by both narrow and broad specificity proteinases, has been generated yielding a robust data set of strictly limited sites. A critical evaluation of an expanded set of conformational parameters revealed a strong correlation with limited proteolytic sites, although they are only modest predictors in isolation. The overall predictive power is significantly improved when the conformational parameters are combined in a weighted predictive scheme that permits their relative importance to be compared via a Metropolis search protocol. A subset of the parameters performs equally well demonstrating the key determinants of susceptibility. The derived predictive algorithm has been made available via the internet. Its utility for predicting other surface-correlated features is also discussed.
Original language | English |
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Pages (from-to) | 349-359 |
Number of pages | 10 |
Journal | Protein engineering |
Volume | 11 |
Issue number | 5 |
Publication status | Published - May 1998 |
Keywords
- Limited proteolysis
- Molecular recognition
- Nick-sites
- Prediction
- Proteinase