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对皮蛋白受体的结构洞察力表明amidase活性

Ieva Vasiliauskaité-Brooks¹, Remy Sounier¹, Pascal Rochaix¹

¹Institut de Génomique Fonctionnelle, CNRS UMR-5203 INSERM U1191, University of Montpellier, 34094 Montpellier, France.

|March 23, 2017

概括

皮菌素受体 (ADIPORs) 具有内在的amidase活性. 结构和计算研究揭示了ADIPOR1和ADIPOR2的独特机制,为新的治疗调节器铺平了道路.

科学领域:

生物化学生物化学
结构生物学结构生物学
代谢疾病代谢疾病

背景情况:

亚迪波涅丁受体 (ADIPORs) 是葡萄糖和脂质代谢的关键调节者.
阿迪波尔具有陶酶活性,将陶化物化成斯芬戈和自由脂肪酸 (FFAs).
目前,ADIPOR功能的精确分子机制在很大程度上仍未知.

研究的目的:

为了阐明ADIPOR1和ADIPOR2功能的分子机制.
确定与FFA结合的ADIPOR2的晶体结构,并修改ADIPOR1的结构.
为ADIPORs的amidase活性提出一种机制.

主要方法:

进行X射线晶体学以确定受体结构.
计算方法,包括分子动力学模拟.
生物化学测试以评估amidase活动.

主要成果:

结合FFA的ADIPOR2的晶体结构显示了由adiponectin增强的内在amidase活性.
对ADIPOR的胺结合姿势和拟议的水解机制的识别2.2.
修订后的ADIPOR1结构显示了具有暴露的催化位点的独特架构,也具有内在的amidase活性.
独特的结构特征表明ADIPOR1和ADIPOR2.的不同功能状态或机制.

结论:

ADIPOR1和ADIPOR2具有不同的结构特征和内在的amidase活性.
这些发现为ADIPORs的酶机制提供了洞察力.
这些见解可以指导针对代谢障碍的新型ADIPOR调节器的结构设计.

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