6FKV

Structure and function of aldehyde dehydrogenase from Thermus thermophilus: An enzyme with an evolutionarily-distinct C-terminal arm (Recombinant protein with shortened C-terminal, ADH508)

Summary for 6FKV

• Entry DOI: 10.2210/pdb6fkv/pdb
• Related: 6FJX 6FK3
• Descriptor: Aldehyde dehydrogenase, DI(HYDROXYETHYL)ETHER, SULFATE ION, ... (6 entities in total)
• Functional Keywords: aldehyde dehydrogenase, thermus thermophilus, oxidoreductase
• Biological source: Thermus thermophilus HB27
• Total number of polymer chains: 2
• Total formula weight: 116333.28

Authors

Hayes, K.A.,Noor, M.R.,Djeghader, A.,Soulimane, T. (deposition date: 2018-01-24, release date: 2018-09-26, Last modification date: 2024-01-17)

Primary citation

Hayes, K.,Noor, M.,Djeghader, A.,Armshaw, P.,Pembroke, T.,Tofail, S.,Soulimane, T.
The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension.
Sci Rep, 8:13327-13327, 2018

PubMed Abstract: 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) 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 and stabilizing termini-interactions, the current model of tail-mediated substrate access is not apparent in ALDH. The discovery of such a long tail in a deeply and early branching phylum such as Deinococcus-Thermus indicates that ALDH 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.

PubMed: 30190503
DOI: 10.1038/s41598-018-31724-8

Experimental method

X-RAY DIFFRACTION (2.9 Å)