Nicotinamidase from the thermophilic archaeon Acidilobus saccharovorans: structural and functional characteristics

Biochemistry (Mosc). 2014 Jan;79(1):54-61. doi: 10.1134/S0006297914010088.

Abstract

Nicotinamidase is involved in the maintenance of NAD+ homeostasis and in the NAD+ salvage pathway of most prokaryotes, and it is considered as a possible drug target. The gene (ASAC_0847) encoding a hypothetical nicotinamidase has been found in the genome of the thermophilic archaeon Acidilobus saccharovorans. The product of this gene, NA_As0847, has been expressed in Escherichia coli, isolated, and characterized as a Fe(2+)-containing nicotinamidase (k(cat)/K(m) = 427 mM(-1)·sec(-1))/pyrazinamidase (k(cat)/K(m) = 331 mM(-1)·sec(-1)). NA_As0847 is a homodimer with molecular mass 46.4 kDa. The enzyme has high thermostability (T(1/2) (60°C) = 180 min, T(1/2) (80°C) = 35 min) and thermophilicity (T(opt) = 90°C, E(a) = 30.2 ± 1.0 kJ/mol) and broad pH interval of activity, with the optimum at pH 7.5. Special features of NA_As0847 are the presence of Fe2+ instead of Zn2+ in the active site of the enzyme and inhibition of the enzyme activity by Zn2+ at micromolar concentrations. Analysis of the amino acid sequence revealed a new motif of the metal-binding site (DXHXXXDXXEXXXWXXH) for homological archaeal nicotinamidases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Catalytic Domain
  • Crenarchaeota / enzymology*
  • Crenarchaeota / genetics
  • Dimerization
  • Escherichia coli / metabolism
  • Genome, Archaeal
  • Ions / chemistry
  • Kinetics
  • Molecular Sequence Data
  • Nicotinamidase / chemistry
  • Nicotinamidase / genetics
  • Nicotinamidase / metabolism*
  • Protein Stability
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Sequence Alignment
  • Temperature
  • Zinc / chemistry
  • Zinc / metabolism

Substances

  • Archaeal Proteins
  • Ions
  • Recombinant Proteins
  • Nicotinamidase
  • Zinc