Structural and biochemical studies on aldehyde-alcohol dehydrogenase of Vibrio cholerae

Abstract

Aldehyde-alcohol dehydrogenase (AdhE) is a metabolic enzyme and virulence factor in bacteria. E. coli AdhE (eAdhE) multimerizes into spirosomes that are essential for enzymatic activity. However, it is unknown whether AdhE structure is conserved in divergent bacteria. Here, I present the cryo-EM structure of AdhE (vAdhE) from Vibrio cholerae to 4.31 Å resolution. Overall, vAdhE spirosomes are similar to eAdhE with conserved subunit arrangement. However, vAdhE spirosome has a lower stability compared to eAdhE. I found that divergences in key oligomerization residues cause vAdhE to form labile spirosomes with lower enzymatic activity. Mutating the vAdhE oligomerization interface to mimic eAdhE increases spirosome stability and enzymatic activity to levels comparable to eAdhE. These results support the generality of AdhE spirosome structures, and provide a structural basis to target vAdhE to attenuate bacterial virulence.