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高分辨率的双视图的全性酸酶 PTP1B

Shivani Sharma¹, Tamar Skaist Mehlman¹, Reddy Sudheer Sagabala²

¹Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA.

Acta crystallographica. Section F, Structural biology communications

|December 22, 2023

概括

高分辨率晶体学揭示了野生类型蛋白氨酸酸酶1B (PTP1B) 中不同的构造状态. 这些发现阐明了PTP1BB.

科学领域:

生物化学和结构生物学.
蛋白质动态和全调节的调节.
结晶学和结构分析.

背景情况:

蛋白氨酸酸酶1B (PTP1B) 是细胞平衡的关键调节剂,也是糖尿病,肥胖和癌症的治疗点.
了解PTP1B的构造变化对于阐明其全调节和对突变的功能反应至关重要.

研究的目的:

为了呈现迄今为止最高分辨率的Apo野生型 (WT) PTP1B晶体结构.
用高分辨率晶体学研究PTP1B内部的形状异质性.
为了比较apo WT PTP1B和联体结合结构之间的构造差异,并检查突变结构.

主要方法:

野生类型 (WT) PTP1B的高分辨率X射线晶体学.
蛋白质构成组合和异质性的分析.
从apo,联体结合和突变PTP1B结构的结晶学数据的比较.

主要成果:

获得了一种罕见的Apo WT PTP1B晶体形式,揭示了具有明显构造异质性的两个独特蛋白质副本.
在apo结构中观察到两个链之间的形状差异,并与结合体结合的结构进行比较.
在激活的双重突变结构中确定了未建模的替代构造,与WT PTP1B.中增强的异质性相吻合.

结论:

PTP1B中的突变可能会增强局部动力学,这表明WT酶具有固有的敏感性.
高分辨率晶体学有效阐明了PTP1B的形状组合和异质性.
这些发现为PTP1B的功能机制和潜在的治疗调制提供了洞察力.

关键词:

全osteric调节的调节.构成性的异质性构成性的异质性高分辨率的晶体学.蛋白质氨酸酸酶1B的蛋白质氨酸酸酶1B.

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