Aldehyde-alcohol dehydrogenase undergoes structural transition to form extended spirosomes for substrate channeling

Kim, G., Yang, J., Jang, J., Choi, J.-S., Roe, A. J. , Byron, O. , Seok, C. and Song, J.-J. (2020) Aldehyde-alcohol dehydrogenase undergoes structural transition to form extended spirosomes for substrate channeling. Communications Biology, 3, 298. (doi: 10.1038/s42003-020-1030-1) (PMID:32523125) (PMCID:PMC7286902)

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Abstract

Aldehyde-alcohol dehydrogenase (AdhE) is an enzyme responsible for converting acetyl-CoA to ethanol via acetaldehyde using NADH. AdhE is composed of two catalytic domains of aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH), and forms a spirosome architecture critical for AdhE activity. Here, we present the atomic resolution (3.43 Å) cryo-EM structure of AdhE spirosomes in an extended conformation. The cryo-EM structure shows that AdhE spirosomes undergo a structural transition from compact to extended forms, which may result from cofactor binding. This transition leads to access to a substrate channel between ALDH and ADH active sites. Furthermore, prevention of this structural transition by crosslinking hampers the activity of AdhE, suggesting that the structural transition is important for AdhE activity. This work provides a mechanistic understanding of the regulation mechanisms of AdhE activity via structural transition, and a platform to modulate AdhE activity for developing antibiotics and for facilitating biofuel production.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roe, Professor Andrew and Byron, Professor Olwyn
Authors: Kim, G., Yang, J., Jang, J., Choi, J.-S., Roe, A. J., Byron, O., Seok, C., and Song, J.-J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Communications Biology
Publisher:Nature Research
ISSN:2399-3642
ISSN (Online):2399-3642
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Communications Biology 3: 298
Publisher Policy:Reproduced under a Creative Commons License

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