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The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127216/ https://www.ncbi.nlm.nih.gov/pubmed/30190503 http://dx.doi.org/10.1038/s41598-018-31724-8 |
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author | Hayes, Kevin Noor, Mohamed Djeghader, Ahmed Armshaw, Patricia Pembroke, Tony Tofail, Syed Soulimane, Tewfik |
author_facet | Hayes, Kevin Noor, Mohamed Djeghader, Ahmed Armshaw, Patricia Pembroke, Tony Tofail, Syed Soulimane, Tewfik |
author_sort | Hayes, Kevin |
collection | PubMed |
description | 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 tail-mediated 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. |
format | Online Article Text |
id | pubmed-6127216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61272162018-09-10 The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension Hayes, Kevin Noor, Mohamed Djeghader, Ahmed Armshaw, Patricia Pembroke, Tony Tofail, Syed Soulimane, Tewfik Sci Rep Article 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 tail-mediated 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. Nature Publishing Group UK 2018-09-06 /pmc/articles/PMC6127216/ /pubmed/30190503 http://dx.doi.org/10.1038/s41598-018-31724-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hayes, Kevin Noor, Mohamed Djeghader, Ahmed Armshaw, Patricia Pembroke, Tony Tofail, Syed Soulimane, Tewfik The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title | The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title_full | The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title_fullStr | The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title_full_unstemmed | The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title_short | The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct C-terminal arm extension |
title_sort | quaternary structure of thermus thermophilus aldehyde dehydrogenase is stabilized by an evolutionary distinct c-terminal arm extension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127216/ https://www.ncbi.nlm.nih.gov/pubmed/30190503 http://dx.doi.org/10.1038/s41598-018-31724-8 |
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