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结构洞察到膜中的乌比奎农生物合成

Wei Cheng¹, Weikai Li

¹Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Science (New York, N.Y.)

|February 22, 2014

概括

这种UbiA酶对于ubiquinone生物合成至关重要. 对考古UbiA的结构洞察力揭示了其与膜结合的活性部位,有助于理解先转移酶机制和人类疾病突变.

科学领域:

生物化学生物化学
结构生物学结构生物学
酶学是一种酶学.

背景情况:

乌比基诺 (共酶Q) 是对细胞呼吸至关重要的重要脂性芳香化合物.
该UbiA酶家族,一种前转移酶,催化细胞膜内的乌比金生物合成的关键步骤.
功能障碍的UbiA超级家族成员与人类疾病有关,包括心血管退化和帕金森病.

研究的目的:

通过确定一个古老的UbiA酶的晶体结构来阐明ubiquinone生物合成的结构基础.
了解膜环境中UbiA酶使用的基质识别和催化机制.
为在人类UbiA超级家族成员中观察到的与疾病相关的突变提供结构性理由.

主要方法:

采用X射线晶体学来确定古老的UbiA酶的高分辨率结构,包括其Apo和基质结合形式.
结构分析的重点是识别酶结构的关键特征,包括跨膜螺旋体,外膜域和活性部位腔.
进行了比较分析,以了解脂质双层内的基质可访问性和催化机制.

主要成果:

晶体结构揭示了9个跨膜螺旋结构与外膜盖域,封闭一个中央活跃点腔.
确定了一个独特的,侧向打开的活性部位,促进与脂质双层和基板的直接相互作用.
这些结构提供了详细的洞察力,可以了解酶在基质存在或不存在时的结构.

结论:

确定的结构提供了对UbiA酶如何在生物膜内起作用以合成ubiquinones的机制理解.
这些发现阐明了UbiA prenyltransferase超级家族的基质结合和催化过程的一般原则.
这些结构数据为解释与UbiA超级酶家族突变相关的人类疾病的分子基础提供了基础.

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