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结晶结构确定人类UDP-glucuronosyltransferases2B10核酸糖结合域的结晶结构 2B10

Xinli Yin^1,2, Xi Lu^1,2, Xudan Qi^1,2

¹School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.

Protein and peptide letters

|November 10, 2023

概括

研究人员确定了人类UGT2B10C终端域的高分辨率晶体结构. 这一突破揭示了对药物新陈代谢至关重要的一种保存的辅因子结合口袋.

科学领域:

生物化学生化学
结构生物学结构生物学
药理学药理学是指药理学的学科.

背景情况:

UDP-glucuronosyltransferases (UGTs) 对于代谢药物和内源性化合物至关重要.
阐明UGT催化机制受到缺乏详细的蛋白质结构的阻碍.
人类的UGT,特别是它们的催化领域,在净化和结晶方面面临着挑战.

研究的目的:

阐明人类UGTs的基本催化机制.
为了确定 UGT2B10 C终端辅因子结合域的结构.
提供关于UGT2B10在药物代谢中的作用的结构性见解.

主要方法:

净化和结晶的UGT2B10 C终端域 (CTD).
使用同步辐射 (1.53 Å分辨率) 采集高分辨率的X射线衍射数据.
通过分子替换以同质结构来确定结构.

主要成果:

UGT2B10 CTD 的晶体结构以 1.53 Å 的分辨率得到解决.
这颗晶体属于单临床空间组C2.
在UGT2B10 CTD结构中发现了一个保存的辅因子结合口袋.

结论:

这项研究介绍了人类UGT2B10 C终端辅因子结合域的第一个高分辨率晶体结构.
解决的结构揭示了维护的协因子结合口袋,这对于UGT活动至关重要.
了解这个域的结构是理解UGT2B10在药物代谢中的作用的关键.

关键词:

在UDP-glucuronosyl转移酶2B1010中.添加剂药物新陈代谢.催化机制是一种催化机制.晶体结构晶体结构核酸与糖的结合域是核酸与糖的结合域.同步子辐射是同步子辐射.

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