Inhibition studies with simple and complex (in)organic anions of the γ-carbonic anhydrase from Mammaliicoccus (Staphylococcus) sciuri, MscCAγ

The gamma-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium, Mammaliicoccus (Staphylococcus) sciuri (MscCA gamma) was recently cloned and purified by our groups. Here we investigated inhibition of this enzyme with (in)organic simple and complex anions, in the search of inhibitors with potential applications. The most effective inhibitors (K(I)s in the micromolar range) were peroxydisulfate and trithiocarbonate, whereas submillimolar inhibition was observed with N,N-diethyldithiocarbamate and phenylboronic acid (K(I)s of 0.5-0.9 mM). Thiocyanate, hydrogensulfide, bisulphite, stannate, divanadate, tetraborate, perrhenate, perruthenate, hexafluorophosphate, triflate and iminodisulfonate showed K(I)s of 1.0-13.7 mM. Cyanate, cyanide, azide, carbonate, nitrate, tellurate, selenocyanide, tetrafluoroborate, sulfamide, sulphamic acid and phenylarsonic acid were weaker inhibitors, with K(I)s in the range of 25.2-95.5 mM, whereas halides, bicarbonate, nitrite, sulphate, perchlorate and fluorosulfonate did not show inhibitory action up until 100 mM concentrations in the assay system. Finding more effective MscCA gamma inhibitors may be helpful to fight drug resistance to antibiotics.

Automated summary

The gamma-carbonic anhydrase (CA, EC 4.2.1.1) from Mammaliicoccus (Staphylococcus) sciuri (MscCA gamma) was studied for its inhibition by various (in)organic anions. Peroxydisulfate and trithiocarbonate were the most effective inhibitors, while other anions showed weaker inhibitory effects. Finding more effective MscCA gamma inhibitors could help combat antibiotic resistance.