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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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Subsite cooperativity in protease specificity

Natasha M. Ng
  • Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Robert N. Pike
  • Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sarah E. Boyd
  • Clayton School of Information Technology, Monash University, Clayton, Victoria 3800, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-04-10 | DOI: https://doi.org/10.1515/BC.2009.065


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 or negative influence on the binding of particular residues at other subsites. This phenomenon has been termed subsite cooperativity and has been observed in a wide range of 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.

Keywords: cooperativity; protease; specificity; subsites

About the article

Corresponding author

Received: 2008-11-25

Accepted: 2009-03-19

Published Online: 2009-04-10

Published in Print: 2009-01-01

Citation Information: Biological Chemistry, Volume 390, Issue 5/6, Pages 401–407, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2009.065.

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