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The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension
Hayes, Kevin; Noor, Mohamed R.; Djeghader, Ahmed; Armshaw, Patricia; Pembroke, Tony J.; Tofail, Syed A.M.; Soulimane, Tewfik
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 (ALDHTt) 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 ALDHTt and stabilizing termini-interactions, the current model of tailmediated substrate access is not apparent in ALDHTt. The discovery of such a long tail in a deeply and early branching phylum such as Deinococcus-Thermus indicates that ALDHTt 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.
Keyword(s): aldehyde dehydrogenases (ALDH)
Publication Date:
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: University of Limerick
Citation(s): info:eu-repo/grantAgreement/EC/FP7/283570
Scientific Reports;8:13327
Publisher(s): Nature Publishing Group
First Indexed: 2018-09-15 06:26:55 Last Updated: 2019-02-13 06:35:03