Peer-Reviewed Journal Details
Mandatory Fields
Hayes, K;Noor, M;Djeghader, A;Armshaw, P;Pembroke, T;Tofail, S;Soulimane, T
2018
September
Scientific Reports
The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension
Published
12 ()
Optional Fields
MITOCHONDRIAL ALDEHYDE DEHYDROGENASE PHOSPHORYLATING GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE CRYSTAL-STRUCTURE MACROMOLECULAR CRYSTALLOGRAPHY SUBSTRATE-SPECIFICITY STRUCTURE REFINEMENT CATALYTIC MECHANISM ANGSTROM RESOLUTION ALPHA-CRYSTALLIN COENZYME
8
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)(+) binding domain, and the oligomerization domain. Here, we describe the structure and function of the ALDH from Thermus thermophilus (ALDH(Tt)) 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(Tt) and stabilizing termini-interactions, the current model of tailmediated substrate access is not apparent in ALDH(Tt). The discovery of such a long tail in a deeply and early branching phylum such as Deinococcus-Thermus indicates that ALDH(Tt) 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.
LONDON
2045-2322
10.1038/s41598-018-31724-8
Grant Details