Aldehyde-alcohol dehydrogenase forms a high-order spirosome architecture critical for its activity

Kim, G., Azmi, L., Jang, S., Jung, T., Hebert, H., Roe, A. J. , Byron, O. and Song, J.-J. (2019) Aldehyde-alcohol dehydrogenase forms a high-order spirosome architecture critical for its activity. Nature Communications, 10, 4527. (doi: 10.1038/s41467-019-12427-8) (PMID:31586059) (PMCID:PMC6778083)

Abstract

Aldehyde-alcohol dehydrogenase (AdhE) is a key enzyme in bacterial fermentation, converting acetyl-CoA to ethanol, via two consecutive catalytic reactions. Here, we present a 3.5 Å resolution cryo-EM structure of full-length AdhE revealing a high-order spirosome architecture. The structure shows that the aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) active sites reside at the outer surface and the inner surface of the spirosome respectively, thus topologically separating these two activities. Furthermore, mutations disrupting the helical structure abrogate enzymatic activity, implying that formation of the spirosome structure is critical for AdhE activity. In addition, we show that this spirosome structure undergoes conformational change in the presence of cofactors. This work presents the atomic resolution structure of AdhE and suggests that the high-order helical structure regulates its enzymatic activity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roe, Professor Andrew and Byron, Professor Olwyn
• Authors: Kim, G., Azmi, L., Jang, S., Jung, T., Hebert, H., Roe, A. J., Byron, O., and Song, J.-J.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Nature Communications 10:4527
• Publisher Policy: Reproduced under a Creative Commons License