Inhibition studies with anions and small molecules of two novel β-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3591-5. doi: 10.1016/j.bmcl.2011.04.105. Epub 2011 Apr 28.

Abstract

Two new β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Salmonella enterica serovar Typhimurium, stCA 1 and stCA 2, were characterized kinetically. The two enzymes possess appreciable activity as catalysts for the hydration of CO(2) to bicarbonate, with k(cat) of 0.79×10(6) s(-1) and 1.0×10(6) s(-1), and k(cat)/K(m) of 5.2×10(7) M(-1) s(-1) and of 8.3×10(7) M(-1) s(-1), respectively. A large number of simple/complex inorganic anions as well as other small molecules (sulfamide, sulfamic acid, phenylboronic acid, phenylarsonic acid, dialkyldithiocarbamates) showed interesting inhibitory properties towards the two new enzymes, with several low micromolar inhibitors discovered. As many strains of S. enterica show extensive resistance to classical antibiotics, inhibition of the β-CAs investigated here may be useful for developing lead compounds for novel types of antibacterials.

MeSH terms

  • Amino Acid Sequence
  • Anions / chemical synthesis
  • Anions / chemistry*
  • Anions / pharmacology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / isolation & purification
  • Carbonic Anhydrases / pharmacology*
  • Enzyme Activation / drug effects
  • Molecular Sequence Data
  • Salmonella typhimurium / enzymology*
  • Sequence Alignment

Substances

  • Anions
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrases