Istituto di Biochimica delle Proteine-CNR, Via P. Castellino 111, 80131 Napoli, Italy.
J Med Chem. 2012 Dec 13;55(23):10742-8. doi: 10.1021/jm301611m. Epub 2012 Dec 4.
We have cloned, purified, and characterized an α-carbonic anhydrase (CA, EC 4.2.1.1) from the human pathogenic bacterium Vibrio cholerae, VchCA. The new enzyme has significant catalytic activity, and an inhibition study with sulfonamides and sulfamates led to the detection of a large number of low nanomolar inhibitors, among which are methazolamide, acetazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, and indisulam (KI values in the range 0.69-8.1 nM). As bicarbonate is a virulence factor of this bacterium and since ethoxzolamide was shown to inhibit the in vivo virulence, we propose that VchCA may be a target for antibiotic development, exploiting a mechanism of action rarely considered until now.
我们从人类病原体霍乱弧菌（Vibrio cholerae）中克隆、纯化并鉴定了一种α-碳酸酐酶（CA，EC 4.2.1.1），即 VchCA。该新型酶具有显著的催化活性，对磺胺类和磺胺酸盐的抑制研究检测到了大量低纳摩尔级的抑制剂，其中包括甲唑胺、乙酰唑胺、依索唑胺、多佐胺、布林佐胺、苯佐胺和异噁唑磺胺（KI 值在 0.69-8.1 nM 范围内）。由于碳酸氢盐是该细菌的一种毒力因子，且依索唑胺已被证明能够抑制体内毒力，我们提出 VchCA 可能是抗生素开发的一个靶点，利用一种迄今为止很少被考虑的作用机制。
