High-resolution structure of alcohol dehydrogenase from the bifunctional bacterial enzyme AdhE
Liyana Azmi, Eilis C. Bragginton, Ian T. Cadby, Olwyn Byron, Andrew J. Roe, Andrew L. Lovering and Mads Gabrielsen [1]
Molecular Tour
The bifunctional aldehyde/alcohol dehydrogenase (AdhE) is a protein of many uses. Genomic studies showed that AdhE is a viable target for anti-virulence compounds. On the other hand, residual mutations of AdhE led to the increased production of ethanol for biofuel generation. Thus, structural information of AdhE is crucial for the genetic modification of the protein to enhance biofuel production and allow structure-based drug design for anti-virulence therapies.
AdhE is an interesting protein by the virtue of its structural assembly. Multiple copies of AdhE self-oligomerises to form spiral protomers known as spirosomes. However, the heterogeneity of these spirosomes make structural characterisation complex thus, separation of the domains allows more structural and biochemical depiction of AdhE.
Here, we have individually characterised the structure of the N-terminal, alcohol dehydrogenase (ADH). ADH crystallised with a homodimer formation, which is also adopted in the spirosome assembly in AdhE. Interestingly, this conformation is also highly conserved with other alcohol dehydrogenases in other species. Comparison to the high-resolution structure of AdhE showed that a missing loop in ADH is stabilised by the C-terminal aldehyde dehydrogenase and shows the importance of the interaction for the functionality of AdhE as a whole.
. The two subdomains are coloured slate (N-terminal) and teal (C-terminal), with NAD represented by green sticks and Fe2+ ions by orange spheres (PDB entry 6scg).
, in which the two subunits forming the dimer are coloured separately.
(PDB entry 6ahc).
. Water molecules are shown as red spheres.
PDB references: alcohol dehydrogenase domain of AdhE, 6sci; NAD-bound, 6scg
References
- ↑ Azmi L, Bragginton EC, Cadby IT, Byron O, Roe AJ, Lovering AL, Gabrielsen M. High-resolution structure of the alcohol dehydrogenase domain of the bifunctional bacterial enzyme AdhE. Acta Crystallogr F Struct Biol Commun. 2020 Sep 1;76(Pt 9):414-421. doi:, 10.1107/S2053230X20010237. Epub 2020 Aug 19. PMID:32880589 doi:http://dx.doi.org/10.1107/S2053230X20010237
