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

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Vullo D, Nishimori I, Minakuchi T, Scozzafava A, Supuran CT

Inhibition studies with anions and small molecules of two novel beta-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.

PubMed ID

21570835 [ View in PubMed

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Abstract

Two new beta-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 0.79x10(6) s(-1) and 1.0x10(6) s(-1), and k(cat)/K(m) of 5.2x10(7) M(-1) s(-1) and of 8.3x10(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 beta-CAs investigated here may be useful for developing lead compounds for novel types of antibacterials.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details