Schlee, Sandra and Straub, Kristina and Schwab, Thomas and Kinateder, Thomas and Merkl, Rainer and Sterner, Reinhard (2019) Prediction of quaternary structure by analysis of hot spot residues in protein-protein interfaces: the case of anthranilate phosphoribosyltransferases. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 87 (10). pp. 815-825. ISSN 0887-3585, 1097-0134
Full text not available from this repository. (Request a copy)Abstract
It is an important goal of computational biology to correctly predict the association state of a protein based on its amino acid sequence and the structures of known homologues. We have pursued this goal on the example of anthranilate phosphoribosyltransferase (AnPRT), an enzyme that is involved in the biosynthesis of the amino acid tryptophan. Firstly, known crystal structures of naturally occurring homodimeric AnPRTs were analyzed using the Protein Interfaces, Surfaces, and Assemblies (PISA) service of the European Bioinformatics Institute (EBI). This led to the identification of two hydrophobic "hot spot" amino acids in the protein-protein interface that were predicted to be essential for self-association. Next, in a comprehensive multiple sequence alignment (MSA), naturally occurring AnPRT variants with hydrophilic or charged amino acids in place of hydrophobic residues in the two hot spot positions were identified. Representative variants were characterized in terms of thermal stability, enzymatic activity, and quaternary structure. We found that AnPRT variants with charged residues in both hot spot positions exist exclusively as monomers in solution. Variants with hydrophilic amino acids in one hot spot position occur in both forms, monomer and dimer. The results of the present study provide a detailed characterization of the determinants of the AnPRT monomer-dimer equilibrium and show that analysis of hot spots in combination with MSAs can be a valuable tool in prediction of protein quaternary structures.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SULFOLOBUS-SOLFATARICUS; MUTATIONAL ANALYSIS; STABILITY; SUBSTRATE; ENZYME; CONSERVATION; SOLUBILITY; ACTIVATION; EXPRESSION; VARIANTS; anthranilate phosphoribosyltransferase; hot spots; multiple sequence alignment; protein-protein interface |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2020 08:18 |
| Last Modified: | 27 Mar 2020 08:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26196 |
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