期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 25, 期 17, 页码 4800-4804出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.07.033
关键词
Carbonic anhydrase; beta-Class; CA inhibitors; Anions; Francisella tularensis; Tularemia
资金
- European Union [HEALTH-F2-2010-261460]
- Distinguished Scientist Fellowship Program (DSFP) of King Saud University, Riyadh, Saudi Arabia
- Australian Research Council [DP160102681]
A beta-class carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Francisella tularensis (Ftu beta CA) was cloned and purified, and the anion inhibition profile was investigated. Based on the measured kinetic parameters for the enzyme catalyzed CO2 hydration reaction (k(cat) of 9.8 x 10(5) s(-1) and a loot/K-M of 8.9 x 10(7) M-1 s(-1)), Ftu beta CA is a highly effective enzyme. The activity of Ftu beta CA was not inhibited by a range of anions that do not typically coordinate Zn(II) effectively, including perchlorate, tetrafluoroborate, and hexafluorophosphate. Surprisingly, some anions which generally complex well with many cations, including Zn(II), also did not effectively inhibit FtuBCA, e.g., fluoride, cyanide, azide, nitrite, bisulphite, sulfate, tellurate, perrhenate, perrhuthenate, and peroxydisulfate. However, the most effective inhibitors were in the range of 90-94 tiM (sulfamide, sulfamic acid, phenylarsonic and phenylboronic acid). N,N-Diethyldithiocarbamate (K-I of 0.31 mM) was a moderately potent inhibitor. As Francisella tularensis is the causative agent of tularemia, the discovery of compounds that can interfere with the life cycle of this pathogen may result in novel opportunities to fight antibiotic drug resistance. (C) 2017 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据