Molecular recognition: Conformational analysis of limited proteolytic sites and serine proteinase protein inhibitors

S. J. Hubbard, S. F. Campbell, J. M. Thornton

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The conformations of known tryptic limited proteolytic sites have been analysed and compared to the structures of the binding regions of serine proteinase inhibitors, as they are found when complexed to a serine proteinase. Conformational parameters studied include main-chain torsion angles, root-mean-square fits, accessibility, mobility and protrusion indices. As observed before, the inhibitors share a common main-chain conformation at the binding loop from P3-P'3 (Schechter & Berger notation), which is maintained throughout all the serine proteinase inhibitor families for which X-ray data is available, despite lack of similarity in the rest of the protein. This canonical structure is not found amongst the limited proteolytic sites (or nicksites), which differ markedly from the inhibitor binding loop conformation, and also amongst themselves. The experimentally determined nicksites are in general both accessible and protruding; as are the inhibitor binding loops, as well as being typically flexible regions of structure, as denoted by elevated temperature factors from crystallographic determinations. For cleavage by serine proteinases- these loops must radically alter their local conformations and a large motion of the loop relative to the structure, in some cases, would be required to orientate these sites for cleavage. © 1991 Academic Press Limited.
    Original languageEnglish
    Pages (from-to)507-530
    Number of pages23
    JournalJournal of molecular biology
    Volume220
    Issue number2
    DOIs
    Publication statusPublished - 1991

    Keywords

    • Flexibility
    • Inhibitor
    • Nicksite
    • Proteinase
    • Recognition

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