化学
肽
功能(生物学)
差向异构体
生物化学
酶
基因
苯丙氨酸
氨基酸
计算生物学
生物
机制(生物学)
立体化学
蛋白质结构
遗传学
蛋白质结构域
蛋白质功能
蛋白质-蛋白质相互作用
色氨酸
基因家族
翻译后修饰
肽序列
肽键
血浆蛋白结合
肽生物合成
肽合成
分子模型
反作用
三域系统
作者
Menghan Shi,Yuwei Duan,Hou Shao-yang,Liangxu Xie,Wei Sun,Liubin Feng,Youming Zhang,Xiaoying Bian,Guannan Zhong
出处
期刊:ACS Catalysis
[American Chemical Society]
日期:2026-01-01
卷期号:16 (2): 1757-1772
被引量:1
标识
DOI:10.1021/acscatal.5c08590
摘要
The domain of unknown function 6895 (DUF6895) constitutes a poorly characterized protein family. Its functional obscurity positions this family of proteins as high-value targets to unlock cryptic enzymatic activities and molecular mechanisms. Here, we identified a DUF6895-encoding gene within a lasso peptide biosynthetic gene cluster. The DUF6895 protein ShpE functions as a distinct epimerase that inverts the configuration of phenylalanine in the linear precursor peptide, a modification essential for the subsequent tryptophan dihydroxylation. Structural and mechanistic analyses demonstrated that ShpE provides a hydrophobic cavity to accommodate phenylalanine and employs acid–base chemistry to facilitate reversible epimerization via dual His/Glu catalytic dyads. These dyads are evolutionarily conserved across DUF6895 proteins, suggesting the majority of these family members function as epimerases through a common molecular mechanism. Our work on ShpE expands the enzymatic repertoire for epimerization in ribosomally synthesized and post-translationally modified peptides (RiPPs), providing crucial insights into the function and mechanism of the neglected DUF6895 proteins.
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