Predicting serpin/protease interactions Academic Article uri icon

abstract

  • 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.

authors

  • Song, J
  • Matthews, AY
  • Reboul, CF
  • Kaiserman, D
  • Pike, RN
  • Bird, PI
  • Whisstock, JC

publication date

  • 2011