Nicotinamide mononucleotide (NMN) is a key intermediate in the nicotinamide adenine dinucleotide (NAD+) biosynthesis. Its supplementation has demonstrated beneficial effects on several diseases. The aim of this study was to characterize NMN deamidase (PncC) inactive mutants to use as possible molecular recognition elements (MREs) for an NMN-specific biosensor. Thermal stability assays and steady-state fluorescence spectroscopy measurements were used to study the binding of NMN and related metabolites (NaMN, Na, Nam, NR, NAD, NADP, and NaAD) to the PncC mutated variants. In particular, the S29A PncC and K61Q PncC variant forms were selected since they still preserve the ability to bind NMN in the micromolar range, but they are not able to catalyze the enzymatic reaction. While S29A PncC shows a similar affinity also for NaMN (the product of the PncC catalyzed reaction), K61Q PncC does not interact significantly with it. Thus, PncC K61Q mutant seems to be a promising candidate to use as specific probe for an NMN biosensor.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231969 | PMC |
| http://dx.doi.org/10.3390/ijms22126334 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Biotechnological production of reduced and oxidized NAD precursors.
Food Res Int
March 2023
Department of Biochemistry and Molecular Biology-A, University of Murcia, Murcia, Spain. Electronic address:
Dysregulation of nicotinamide adenine dinucleotide (NAD) homeostasis by increased activity of NAD consumers or reduced NAD biosynthesis plays an important role in the onset of prevalent, often age-related, diseases, such as diabetes, neuropathies or nephropathies. To counteract such dysregulation, NAD replenishment strategies can be used. Among these, administration of vitamin B derivatives (NAD precursors) has garnered attention in recent years.
View Article and Find Full Text PDFThe NAD precursor NMN activates dSarm to trigger axon degeneration in .
Elife
December 2022
Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
Axon degeneration contributes to the disruption of neuronal circuit function in diseased and injured nervous systems. Severed axons degenerate following the activation of an evolutionarily conserved signaling pathway, which culminates in the activation of SARM1 in mammals to execute the pathological depletion of the metabolite NAD. SARM1 NADase activity is activated by the NAD precursor nicotinamide mononucleotide (NMN).
View Article and Find Full Text PDFNicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection.
Exp Neurol
November 2021
Washington University School of Medicine in Saint Louis, Department of Genetics, St. Louis, MO, USA; Needleman Center for Neurometabolism and Axonal Therapeutics, USA.
SARM1 is an inducible NAD hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site within the SARM1 N-terminal ARM domain. In healthy neurons with abundant NAD, binding of NAD blocks access of NMN to this allosteric site.
View Article and Find Full Text PDFCharacterization of Two NMN Deamidase Mutants as Possible Probes for an NMN Biosensor.
Int J Mol Sci
June 2021
Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy.
Nicotinamide mononucleotide (NMN) is a key intermediate in the nicotinamide adenine dinucleotide (NAD+) biosynthesis. Its supplementation has demonstrated beneficial effects on several diseases. The aim of this study was to characterize NMN deamidase (PncC) inactive mutants to use as possible molecular recognition elements (MREs) for an NMN-specific biosensor.
View Article and Find Full Text PDFPharmacological bypass of NAD salvage pathway protects neurons from chemotherapy-induced degeneration.
Proc Natl Acad Sci U S A
October 2018
Vollum Institute, Oregon Health & Science University, Portland, OR 97239;
Axon degeneration, a hallmark of chemotherapy-induced peripheral neuropathy (CIPN), is thought to be caused by a loss of the essential metabolite nicotinamide adenine dinucleotide (NAD) via the prodegenerative protein SARM1. Some studies challenge this notion, however, and suggest that an aberrant increase in a direct precursor of NAD, nicotinamide mononucleotide (NMN), rather than loss of NAD, is responsible. In support of this idea, blocking NMN accumulation in neurons by expressing a bacterial NMN deamidase protected axons from degeneration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!