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

• DOI: 10.1038/s42003-020-1030-1
• Publication Date: 2020-06-10T10:03:15Z
• Authors: Gijeong Kim; Jinsol Yang; Juwon Jang; Jin-Seok Choi; Andrew J. Roe; Olwyn Byron; Chaok Seok; Ji-Joon Song
• Keywords: Models, Molecular; Organelles; Aldehydes; 0303 health sciences; Ethanol; Protein Conformation; Escherichia coli Proteins; Cryoelectron Microscopy; Alcohol Dehydrogenase; Crystallography, X-Ray; Aldehyde Oxidoreductases; Article; Substrate Specificity; 03 medical and health sciences; Escherichia coli

AbstractAldehyde-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.