结核分枝杆菌乙酰乳酸合酶（IlvH）调节亚基Rv3002c的表达、纯化及初步晶体学分析
Expression, purification and preliminary crystallographic analysis of Rv3002c, the regulatory subunit of acetolactate synthase (IlvH) from Mycobacterium tuberculosis.
作者信息
Yin Jiang, Garen Grace, Garen Craig, James Michael N G
机构信息
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Aug 1;67(Pt 8):933-6. doi: 10.1107/S1744309111021105. Epub 2011 Jul 20.
Abstract
Branched amino-acid biosynthesis is important to bacterial pathogens such as Mycobacterium tuberculosis (Mtb), a microorganism that presently causes more deaths in humans than any other prokaryotic pathogen (http://www.who.int/tb). In this study, the molecular cloning, expression, purification, crystallization and preliminary crystallographic analysis of recombinant IlvH, the small regulatory subunit of acetohydroxylic acid synthase (AHAS) in Mtb, are reported. AHAS carries out the first common reaction in the biosynthesis of valine, leucine and isoleucine. AHAS is an essential enzyme in Mtb and its inactivation leads to a lethal phenotype [Sassetti et al. (2001), Proc. Natl Acad. Sci. USA, 98, 12712-12717]. Thus, inhibitors of AHAS could potentially be developed into novel anti-Mtb therapies.
摘要
支链氨基酸的生物合成对于诸如结核分枝杆菌（Mtb）这样的细菌病原体很重要，这种微生物目前在人类中造成的死亡比任何其他原核病原体都多（http://www.who.int/tb）。在本研究中，报道了结核分枝杆菌中乙酰羟酸合酶（AHAS）的小调节亚基重组IlvH的分子克隆、表达、纯化、结晶及初步晶体学分析。AHAS在缬氨酸、亮氨酸和异亮氨酸的生物合成中催化第一个共同反应。AHAS是结核分枝杆菌中的一种必需酶，其失活会导致致死表型[Sassetti等人（2001年），《美国国家科学院院刊》，98，12712 - 12717]。因此，AHAS抑制剂有可能被开发成新型抗结核分枝杆菌疗法。
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