The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension

  • Sci Rep. 2018 Sep 6;8(1):13327. doi: 10.1038/s41598-018-31724-8.
Kevin Hayes  1  2 ,  Mohamed Noor  1  2 ,  Ahmed Djeghader  1  2 ,  Patricia Armshaw  1  2 ,  Tony Pembroke  1  2 ,  Syed Tofail  2  3 ,  Tewfik Soulimane  4  5
Affiliations
  • 1. Department of Chemical Sciences, University of Limerick, Limerick, V94 T9PX, Ireland.
  • 2. Bernal Institute, University of Limerick, Limerick, V94 T9PX, Ireland.
  • 3. Physics Department, University of Limerick, Limerick, V94 T9PX, Ireland.
  • 4. Department of Chemical Sciences, University of Limerick, Limerick, V94 T9PX, Ireland. [email protected].
  • 5. Bernal Institute, University of Limerick, Limerick, V94 T9PX, Ireland. [email protected].
PMID: 30190503 DOI: 10.1038/s41598-018-31724-8
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 (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 tail-mediated 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.

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