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Electrostatic recognition in substrate binding to serine proteases
Author(s) -
Waldner Birgit J.,
Kraml Johannes,
Kahler Ursula,
Spinn Alexander,
Schauperl Michael,
Podewitz Maren,
Fuchs Julian E.,
Cruciani Gabriele,
Liedl Klaus R.
Publication year - 2018
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2727
Subject(s) - proteases , electrostatics , substrate (aquarium) , serine , amino acid , chemistry , chymotrypsin , serine protease , static electricity , molecular recognition , protease , enzyme , biochemistry , trypsin , biology , physics , molecule , organic chemistry , ecology , quantum mechanics
Serine proteases of the Chymotrypsin family are structurally very similar but have very different substrate preferences. This study investigates a set of 9 different proteases of this family comprising proteases that prefer substrates containing positively charged amino acids, negatively charged amino acids, and uncharged amino acids with varying degree of specificity. Here, we show that differences in electrostatic substrate preferences can be predicted reliably by electrostatic molecular interaction fields employing customized GRID probes. Thus, we are able to directly link protease structures to their electrostatic substrate preferences. Additionally, we present a new metric that measures similarities in substrate preferences focusing only on electrostatics. It efficiently compares these electrostatic substrate preferences between different proteases. This new metric can be interpreted as the electrostatic part of our previously developed substrate similarity metric. Consequently, we suggest, that substrate recognition in terms of electrostatics and shape complementarity are rather orthogonal aspects of substrate recognition. This is in line with a 2‐step mechanism of protein‐protein recognition suggested in the literature.