Electrostatic recognition in substrate binding to serine proteases
Autor: | Ursula Kahler, Birgit J. Waldner, Maren Podewitz, Alexander Spinn, Klaus R. Liedl, Gabriele Cruciani, Johannes Kraml, Julian E. Fuchs, Michael Schauperl |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Proteases medicine.medical_treatment Static Electricity Substrate recognition substrate 010402 general chemistry 01 natural sciences Substrate Specificity Serine 03 medical and health sciences Structural Biology medicine Molecular interaction fields Molecular Biology Research Articles chemistry.chemical_classification electrostatic similarity Binding Sites Protease Chymotrypsin biology substrate recognition encounter complex molecular interaction fields protease Electrostatics 0104 chemical sciences Amino acid 030104 developmental biology chemistry biology.protein Biophysics Serine Proteases Research Article Protein Binding |
Zdroj: | Journal of Molecular Recognition |
Popis: | 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. |
Databáze: | OpenAIRE |
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