在小的prolyl异构酶中发现一个扩展的结网的晶体学证明
Jonathan W Mueller1, Nina M Link, Anja Matena
1Institute for Structural and Medicinal Biochemistry, Center for Medical Biotechnology (ZMB), University of Duisburg-Essen, 45117 Essen, Germany.
Journal of the American Chemical Society
|November 16, 2011
概括
帕林是帮助蛋白质正确折叠的小酶. 一个新的晶体结构揭示了一个保存的催化四级,包括一个以前未被识别的氨酸残留物,对酶功能至关重要.
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:
- 帕林是一种小基-基异构酶 (PPIases) 的类,对于蛋白质折叠和质量控制至关重要.
- 催化腔中的关键氨基酸被保存,但它们在催化中的具体作用尚不清楚.
研究的目的:
- 通过确定Par14的高分辨率晶体结构来阐明parvulins的催化机制.
- 识别和描述催化场内的氨基酸残留的功能意义.
主要方法:
- 高分辨率 (0.8 Å) 的X射线晶体学的帕鲁林Par14的prolyl异构酶域.
- 分析电子密度图以可视化原子位置.
- 位点定向突变发生 (Pin1的T152A突变),以评估催化活性和蛋白质稳定性.
主要成果:
- 晶体结构揭示了位于D74,H42,H123和T118.8侧链之间原子的电子密度.
- 一个氨酸残留物 (T118在Par14,T152在Pin1) 被确定为催化四位数的一部分,这个角色以前没有被认可.
- 一种Pin1的T152A突变体显著减少了催化活性,同时保持了蛋白质的稳定性.
结论:
- 保存的催化四位数 (D74,H42,H123,T118) 是帕武林和Pin1型基基基异构酶的一个共同特征.
- 鉴定到的氨酸残留物在这些酶的催化机制中起着关键作用.
- 这一发现促进了对PPIase功能在蛋白质折叠和质量控制中的分子基础的理解.
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