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嗜热硫氢光合菌(Sulfurihydrogenibium yellowstonense YO3AOP1)的阿尔法碳酸酐酶极易受到磺胺类药物的抑制。

The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.

机构信息

Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.

出版信息

Bioorg Med Chem. 2013 Mar 15;21(6):1534-8. doi: 10.1016/j.bmc.2012.07.024. Epub 2012 Jul 23.

Abstract

The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was investigated for its inhibition with a large series of sulfonamides and a sulfamate, the classical inhibitors of these zinc enzymes. SspCA showed an inhibition profile with these compounds very similar to that of the predominant human cytosolic isoform hCA II, and not to that of the bacterial α-CA from Helicobacter pylori. Some clinically used drugs such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulthiame were low nanomolar SspCA/hCA II inhibitors (KIs in the range of 4.5-12.3nM) whereas simple aromatic/heterocyclic sulfonamides were less effective, micromolar inhibitors. As this highly catalytically active and thermostable enzyme may show biotechnological applications, its inhibition studies may be relevant for designing on/off systems to control its activity.

摘要

新发现的嗜热细菌 Sulfurihydrogenibium yellowstonense YO3AOP1(SspCA)中的α-碳酸酐酶(CA,EC 4.2.1.1)被研究了其与一系列磺胺类药物和磺胺酸盐的抑制作用,这些磺胺类药物和磺胺酸盐是这些锌酶的经典抑制剂。SspCA 对这些化合物的抑制谱与主要的人细胞质同工酶 hCA II 非常相似,而与幽门螺杆菌的细菌α-CA 不同。一些临床使用的药物,如乙酰唑胺、甲唑胺、依索唑胺、二氯苯酰胺、多佐胺、布林佐胺、托吡酯、塞来昔布和硫代乙酰胺,都是低纳摩尔 SspCA/hCA II 的抑制剂(KI 在 4.5-12.3nM 范围内),而简单的芳香族/杂环磺胺类药物的抑制效果则较差,为微摩尔级抑制剂。由于这种具有高度催化活性和热稳定性的酶可能具有生物技术应用,因此其抑制研究可能与设计开/关系统以控制其活性有关。

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