Assessment of conformational parameters as predictors of limited proteolytic sites in native protein structures

S. J. Hubbard, R. J. Beynon, J. M. Thornton

    Research output: Contribution to journalArticlepeer-review

    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 languageEnglish
    Pages (from-to)349-359
    Number of pages10
    JournalProtein engineering
    Volume11
    Issue number5
    Publication statusPublished - May 1998

    Keywords

    • Limited proteolysis
    • Molecular recognition
    • Nick-sites
    • Prediction
    • Proteinase

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