Cleavage Entropy as Quantitative Measure of Protease Specificity

37Citations
Citations of this article
52Readers
Mendeley users who have this article in their library.

Abstract

A purely information theory-guided approach to quantitatively characterize protease specificity is established. We calculate an entropy value for each protease subpocket based on sequences of cleaved substrates extracted from the MEROPS database. We compare our results with known subpocket specificity profiles for individual proteases and protease groups (e.g. serine proteases, metallo proteases) and reflect them quantitatively. Summation of subpocket-wise cleavage entropy contributions yields a measure for overall protease substrate specificity. This total cleavage entropy allows ranking of different proteases with respect to their specificity, separating unspecific digestive enzymes showing high total cleavage entropy from specific proteases involved in signaling cascades. The development of a quantitative cleavage entropy score allows an unbiased comparison of subpocket-wise and overall protease specificity. Thus, it enables assessment of relative importance of physicochemical and structural descriptors in protease recognition. We present an exemplary application of cleavage entropy in tracing substrate specificity in protease evolution. This highlights the wide range of substrate promiscuity within homologue proteases and hence the heavy impact of a limited number of mutations on individual substrate specificity. © 2013 Fuchs et al.

Cite

CITATION STYLE

APA

Fuchs, J. E., von Grafenstein, S., Huber, R. G., Margreiter, M. A., Spitzer, G. M., Wallnoefer, H. G., & Liedl, K. R. (2013). Cleavage Entropy as Quantitative Measure of Protease Specificity. PLoS Computational Biology, 9(4). https://doi.org/10.1371/journal.pcbi.1003007

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free