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

Journal of enzyme inhibition and medicinal chemistry(2023)

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摘要
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.
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关键词
Staphylococcaceae,carbonic anhydrase,inhibitor,anion,Mammaliicoccus (Staphylococcus) sciuri
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