Predicting serpin/protease interactions

Jiangning Song, Antony Matthews, Cyril F Reboul, Dion Kaiserman, Robert N Pike, Phillip I Bird, James C Whisstock

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

9 Citations (Scopus)


Proteases are tightly regulated by specific inhibitors, such as serpins, which are able to undergo considerable and irreversible conformational changes in order to trap their targets. There has been a considerable effort to investigate serpin structure and functions in the past few decades; however, the specific interactions between proteases and serpins remain elusive. In this chapter, we describe detailed experimental protocols to determine and characterize the extended substrate specificity of proteases based on a substrate phage display technique. We also describe how to employ a bioinformatics system to analyze the substrate specificity data obtained from this technique and predict the potential inhibitory serpin partners of a protease (in this case, the immune protease, granzyme B) in a step-by-step manner. The method described here could also be applied to other proteases for more generalized substrate specificity analysis and substrate discovery.
Original languageEnglish
Title of host publicationMethods in Enzymology, Volume 501: Serpin Structure and Evolution
EditorsJames C Whisstock, Philip I Bird
Place of PublicationUSA
PublisherAcademic Press
Pages237 - 273
Number of pages37
ISBN (Print)9780123859501
Publication statusPublished - 2011

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