Structure and function of nicotinamide mononucleotide adenylyltransferase.
The enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT), a member of the nucleotidyltransferase alpha/beta phosphodiesterase superfamily, catalyzes the reaction NMN + ATP = NAD + PPi, representing the final step in the biosynthesis of NAD, a molecule playing a fundamental role as a cofactor in cellular redox reactions. NAD also serves as the substrate for reactions involved in important regulatory roles, such as protein covalent modifications, like ADP-ribosylation reactions, as well as Sir2 histone deacetylase, a recently discovered class of enzymes involved in the regulation of gene silencing. This overview describes the most recent findings on NMNATs from bacteria, archaea, yeast, animal and human sources, with detailed consideration of their major kinetic, molecular and structural features. On this regard, the different characteristics exhibited by the enzyme from the various species are highlighted. The possibility that NMNAT may represent an interesting candidate as a target for the rational design of selective chemotherapeutic agents has been suggested.
Magni
G
G
Istituto di Biotecnologie Biochimiche, Università Politecnica delle Marche, Ancona, Italy. magnig@univpm.it
Amici
A
A
Emanuelli
M
M
Orsomando
G
G
Raffaelli
N
N
Ruggieri
S
S
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009243:NAD / Q000096:biosynthesis / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000737:chemistry / Q000378:metabolism; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009243:NAD; D009537:Nicotinamide Mononucleotide; D000255:Adenosine Triphosphate; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D006655:Histone Deacetylases