Fleming, Jennifer R. and Schupfner, Michael and Busch, Florian and Basle, Arnaud and Ehrmann, Alexander and Sterner, Reinhard and Mayans, Olga (2018) Evolutionary Morphing of Tryptophan Synthase: Functional Mechanisms for the Enzymatic Channeling of Indole. JOURNAL OF MOLECULAR BIOLOGY, 430 (24). pp. 5066-5079. ISSN 0022-2836, 1089-8638
Full text not available from this repository. (Request a copy)Abstract
Tryptophan synthase (TrpS) is a heterotetrameric alpha beta beta alpha enzyme that exhibits complex substrate channeling and allosteric mechanisms and is a model system in enzymology. In this work, we characterize proposed early and late evolutionary states of TrpS and show that they have distinct quaternary structures caused by insertions-deletions of sequence segments (indels) in the beta-subunit. Remarkably, indole hydrophobic channels that connect alpha and beta active sites have re-emerged in both TrpS types, yet they follow different paths through the beta-subunit fold. Also, both TrpS geometries activate the alpha-subunit through the rearrangement of loops flanking the active site. Our results link evolutionary sequence changes in the enzyme subunits with channeling and allostery in the TrpS enzymes. The findings demonstrate that indels allow protein quaternary architectures to escape "minima" in the evolutionary landscape, thereby overcoming the conservational constraints imposed by existing functional interfaces and being free to morph into new mechanistic enzymes. (C) 2018 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 3-DIMENSIONAL STRUCTURE; ALLOSTERIC REGULATION; CLOSED CONFORMATIONS; ALPHA-SUBUNIT; BETA-SUBUNIT; L-SERINE; PROTEIN; COMMUNICATION; BIOSYNTHESIS; INSERTIONS; substrate channeling; enzyme; X-ray crystallography; enzyme evolution; enzyme chimera |
| Subjects: | 500 Science > 530 Physics |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2019 06:47 |
| Last Modified: | 04 Oct 2019 06:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13362 |
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