Subsite cooperativity in protease specificity

Natasha M Ng, Robert Neil Pike, Sarah Elizabeth Boyd

Research output: Contribution to journalArticleResearchpeer-review

51 Citations (Scopus)

Abstract

Proteases play vital roles in a range of biological processes, such as cell cycle, cell growth and differentiation, apoptosis, haemostasis and signalling. Fundamental to our knowledge of protease action is an understanding of how the active site operates; this has been examined through extensive studies of the substrate specificity of the enzymes. Kinetic and structural analyses have shown that the binding of a particular substrate residue at a protease subsite can have either a positive of negative influence on the binding of particular residues at other subsites. This phenomenon has been termed subsite cooperativity and has been seen in a wide range or proteases, often between non-adjacent subsites. This review aims to highlight studies where subsite cooperativity has been observed, experimental techniques used in the past and potential methods that can be employed to comprehensively examine this phenomenon. Further understanding of how the protease active site recognises and chooses its substrates for cleavage will have a significant impact on the development of pharmaceuticals that target these enzymes.
Original languageEnglish
Pages (from-to)401 - 407
Number of pages7
JournalBiological Chemistry
Volume390
Issue number5-6
DOIs
Publication statusPublished - 2009

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