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Exploring NAD+ metabolism and NNAT: Insights from structure, function, and computational modeling
Olamide Jeje1, Sarah Otun1, Chinyere Aloke2
1Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa.
Biochimie
|January 5, 2024
Summary
Nicotinamide Adenine Dinucleotide (NAD+) is vital for cellular processes. Inhibiting the NNAT enzyme in bacteria, which is key to NAD+ biosynthesis, offers a promising strategy against infections like E. faecium and K. pneumoniae.
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- Nicotinamide Adenine Dinucleotide (NAD+) is a crucial coenzyme involved in redox reactions, energy metabolism, and cellular signaling.
- NAD+ metabolism is essential for maintaining cellular functions in both humans and bacteria.
Purpose of the Study:
- To review the structure, function, and biosynthesis of NAD+.
- To explore the role of Nicotinate Nucleotide Adenylyltransferase (NNAT) in NAD+ synthesis.
- To investigate NNAT as a potential therapeutic target against bacterial infections.
Main Methods:
- Review of existing literature on NAD+ metabolism and NNAT.
- Analysis of the de novo synthesis and pyridine ring salvage pathways for NAD+.
- Comparative analysis of human and bacterial NNAT structures and functions.
Main Results:
- NAD+ biosynthesis pathways are conserved between humans and bacteria.
- Bacterial species like E. faecium and K. pneumoniae rely on endogenous NAD+ synthesis.
- NNAT exhibits structural differences between humans and target bacteria, making it a selective target.
Conclusions:
- Inhibiting bacterial NNAT is a viable strategy to combat infections caused by E. faecium and K. pneumoniae.
- Understanding NAD+ metabolism and NNAT's role can lead to novel therapeutic and biotechnological applications.
