Substrate recognition by proteinases

Simon J. Hubbard, Janet M. Thornton, Simon F. Campbell

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The molecular recognition of limited proteolytic site substrates by serine proteinases has been compared and contrasted to the recognition of serine proteinase inhibitors, utilising the coordinate sets contained in the Brookhaven Protein Databank. Most families of these inhibitors are known to possess a structurally conserved recognition motif at their reactive site-binding loops. Structural comparisons with trypsin limited proteolytic sites revealed that the in situ conformation of these substrates bears little resemblance to the inhibitor-binding loops. Assuming that both inhibitors and substrates bind to the proteinase in the same manner, segmental mobility would be required to permit substrates to adopt an 'inhibitor-like' binding conformation, which is presumed to be necessary for proteolysis. Modelling experiments have been conducted to attempt to introduce such a conformation into tryptic limited proteolytic segments of the native proteins, to test the ability of the limited proteolytic sites to alter their geometry. Further to this, the conformational parameters of accessibility, protrusion, mobility and secondary structure have been analysed and incorporated into a predictive algorithm to assign likely limited proteolytic sites within native protein structures.
    Original languageEnglish
    Pages (from-to)13-23
    Number of pages10
    JournalFaraday Discussions
    Volume93
    DOIs
    Publication statusPublished - 1992

    Fingerprint

    Dive into the research topics of 'Substrate recognition by proteinases'. Together they form a unique fingerprint.

    Cite this