Generation of a Stand-Alone Tryptophan Synthase alpha-Subunit by Mimicking an Evolutionary Blueprint

Schupfner, Michael and Busch, Florian and Wysocki, Vicki H. and Sterner, Reinhard (2019) Generation of a Stand-Alone Tryptophan Synthase alpha-Subunit by Mimicking an Evolutionary Blueprint. CHEMBIOCHEM, 20 (21). pp. 2747-2751. ISSN 1439-4227, 1439-7633

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Abstract

The alpha beta beta alpha tryptophan synthase (TS), which is part of primary metabolism, is a paradigm for allosteric communication in multienzyme complexes. In particular, the intrinsically low catalytic activity of the alpha-subunit TrpA is stimulated several hundredfold through the interaction with the beta-subunit TrpB1. The BX1 protein from Zea mays (zmBX1), which is part of secondary metabolism, catalyzes the same reaction as that of its homologue TrpA, but with high activity in the absence of an interaction partner. The intrinsic activity of TrpA can be significantly increased through the exchange of several active-site loop residues, which mimic the corresponding loop in zmBX1. The subsequent identification of activating amino acids in the generated "stand-alone" TrpA contributes to an understanding of allostery in TS. Moreover, findings suggest an evolutionary trajectory that describes the transition from a primary metabolic enzyme regulated by an interaction partner to a self-reliant, stand-alone, secondary metabolic enzyme.

Item Type: Article
Uncontrolled Keywords: ALLOSTERIC REGULATION; SECONDARY METABOLISM; CATALYTIC MECHANISM; GENE; enzymes; molecular evolution; primary metabolism; protein design; secondary metabolism
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner
Depositing User: Dr. Gernot Deinzer
Date Deposited: 31 Mar 2020 09:12
Last Modified: 31 Mar 2020 09:12
URI: https://pred.uni-regensburg.de/id/eprint/26398

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