Exploring NAD + metabolism and NNAT: Insights from structure, function, and computational modeling.

Autor: Jeje O; Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa., Otun S; Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa. Electronic address: oluwatobi.otun@wits.ac.za., Aloke C; Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa; Department of Medical Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, Ebonyi State, Nigeria., Achilonu I; Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2024 May; Vol. 220, pp. 84-98. Date of Electronic Publication: 2024 Jan 03.
DOI: 10.1016/j.biochi.2024.01.002
Abstrakt: Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme, is ubiquitously distributed and serves crucial functions in diverse biological processes, encompassing redox reactions, energy metabolism, and cellular signalling. This review article explores the intricate realm of NAD + metabolism, with a particular emphasis on the complex relationship between its structure, function, and the pivotal enzyme, Nicotinate Nucleotide Adenylyltransferase (NNAT), also known as nicotinate mononucleotide adenylyltransferase (NaMNAT), in the process of its biosynthesis. Our findings indicate that NAD + biosynthesis in humans and bacteria occurs via the same de novo synthesis route and the pyridine ring salvage pathway. Maintaining NAD homeostasis in bacteria is imperative, as most bacterial species cannot get NAD+ from their surroundings. However, due to lower sequence identity and structurally distant relationship of bacteria, including E. faecium and K. pneumonia, to its human counterpart, inhibiting NNAT, an indispensable enzyme implicated in NAD + biosynthesis, is a viable alternative in curtailing infections orchestrated by E. faecium and K. pneumonia. By merging empirical and computational discoveries and connecting the intricate NAD + metabolism network with NNAT's crucial role, it becomes clear that the synergistic effect of these insights may lead to a more profound understanding of the coenzyme's function and its potential applications in the fields of therapeutics and biotechnology.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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