Published:
Springer Science and Business Media LLC, 2018
Published in:
Scientific Reports, 8 (2018) 1
Language:
English
DOI:
10.1038/s41598-018-31724-8
ISSN:
2045-2322
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>Aldehyde dehydrogenases (ALDH) form a superfamily of dimeric or tetrameric enzymes that catalyze the oxidation of a broad range of aldehydes into their corresponding carboxylic acids with the concomitant reduction of the cofactor NAD(P) into NAD(P)H. Despite their varied polypeptide chain length and oligomerisation states, ALDHs possess a conserved architecture of three domains: the catalytic domain, NAD(P)<jats:sup>+</jats:sup> binding domain, and the oligomerization domain. Here, we describe the structure and function of the ALDH from <jats:italic>Thermus thermophilus</jats:italic> (ALDH<jats:sub>Tt</jats:sub>) which exhibits non-canonical features of both dimeric and tetrameric ALDH and a previously uncharacterized C-terminal arm extension forming novel interactions with the N-terminus in the quaternary structure. This unusual tail also interacts closely with the substrate entry tunnel in each monomer providing further mechanistic detail for the recent discovery of tail-mediated activity regulation in ALDH. However, due to the novel distal extension of the tail of ALDH<jats:sub>Tt</jats:sub> and stabilizing termini-interactions, the current model of tail-mediated substrate access is not apparent in ALDH<jats:sub>Tt</jats:sub>. The discovery of such a long tail in a deeply and early branching phylum such as <jats:italic>Deinococcus-Thermus</jats:italic> indicates that ALDH<jats:sub>Tt</jats:sub> may be an ancestral or primordial metabolic model of study. This structure provides invaluable evidence of how metabolic regulation has evolved and provides a link to early enzyme regulatory adaptations.</jats:p>