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

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.

Abstract

Aldehyde-alcohol dehydrogenase (AdhE) converts acetyl-CoA to ethanol and plays an important role in bacterial fermentation. Here the authors present the 3.5 Å cryo-EM structure of full-length E. coli AdhE, which reveals a right-handed helical spirosome structure and they show that the helical structure is required for AdhE activity.