title: Structure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD(+) biosynthesis.
abstract: BACKGROUND
  Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor involved in fundamental processes in cell metabolism. The enzyme nicotinamide mononucleotide adenylyltransferase (NMN AT) plays a key role in NAD(+) biosynthesis, catalysing the condensation of nicotinamide mononucleotide and ATP, and yielding NAD(+) and pyrophosphate. Given its vital role in cell life, the enzyme represents a possible target for the development of new antibacterial agents.
  
  
  RESULTS
  The structure of NMN AT from Methanococcus jannaschii in complex with ATP has been solved by X-ray crystallography at 2.0 A resolution, using a combination of single isomorphous replacement and density modification techniques. The structure reveals a hexamer with 32 point group symmetry composed of alpha/beta topology subunits. The catalytic site is located in a deep cleft on the surface of each subunit, where one ATP molecule and one Mg(2+) are observed. A strictly conserved HXGH motif (in single-letter amino acid code) is involved in ATP binding and recognition.
  
  
  CONCLUSIONS
  The structure of NMN AT closely resembles that of phosphopantetheine adenylyltransferase. Remarkably, in spite of the fact that the two enzymes share the same fold and hexameric assembly, a striking difference in their quaternary structure is observed. Moreover, on the basis of structural similarity including the HXGH motif, we identify NMN AT as a novel member of the newly proposed superfamily of nucleotidyltransferase alpha/beta phosphodiesterases. Our structural data suggest that the catalytic mechanism does not rely on the direct involvement of any protein residues and is likely to be carried out through optimal positioning of substrates and transition-state stabilisation, as is proposed for other members of the nucleotidyltransferase alpha/beta phosphodiesterase superfamily.
authors.affiliation: Department of Genetics and Microbiology 'A. Buzzati Traverso', University of Pavia, via Ferrata 1, 27100, Pavia, Italy.
authors.forename: I
authors.initials: I
authors.lastname: D'Angelo
authors.forename: N
authors.initials: N
authors.lastname: Raffaelli
authors.forename: V
authors.initials: V
authors.lastname: Dabusti
authors.forename: T
authors.initials: T
authors.lastname: Lorenzi
authors.forename: G
authors.initials: G
authors.lastname: Magni
authors.forename: M
authors.initials: M
authors.lastname: Rizzi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D017017:Methanococcus / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000096:biosynthesis; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D021122:Protein Subunits; D009243:NAD; D000255:Adenosine Triphosphate; D009612:Nicotinamide-Nucleotide Adenylyltransferase