致病微生物中对斯福米辛耐药性的机制多样性
Kerry L Fillgrove1, Svetlana Pakhomova, Marcia E Newcomer
1Departments of Biochemistry and Chemistry, Vanderbilt University, Nashville, Tennessee 37232-0146, USA.
Journal of the American Chemical Society
|December 18, 2003
概括
一个新发现的酶组,FosX,通过催化水添加,赋予微生物对抗生素菌素的耐药性. 李斯特菌的FosX酶提供了强大的耐药性,与效率较低的Mesorhizobium loti变种不同.
科学领域:
- 微生物学 微生物学
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- 微生物对色胺素的耐药性主要由FosA和FosB硫醇转移酶介导.
- 通过微生物基因组数据库分析,已经确定了一组新型的酶,称为FosX.
研究的目的:
- 描述新发现的FosX酶家族及其在菌素耐药性中的作用.
- 阐明FosX活动的催化机制和结构基础.
主要方法:
- 从Mesorhizobium loti和Listeria monocytogenes中克隆和表达编码FosX酶的基因.
- 生物化学测试以确定催化效率和基质特异性.
- 确定M. loti FosX. 的晶体结构.
- 位点定向的突变发生和运动分析.
主要成果:
- FosX酶催化了依赖Mn{\displaystyle Mn} 的水添加到斯福米辛中.
- 与M. loti FosX相比,Listeria monocytogenes FosX在大肠杆菌中提供了显著更高的耐药性.
- M. loti FosX 的晶体结构显示了一种催化性谷氨酸残留物 (E44),对于添加水是必不可少的.
- M. loti FosX表现出乱交,也催化了氨酸添加到胺酸中.
结论:
- FosX代表了一种新型的菌素耐药性酶.
- 催化机制涉及E44的一般基催化,促进直接添加水.
- 不同的FosX酶的效率表明,存在一种进化途径,可以对色素产生抗药性.
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