Human Oxygenase Variants Employing a Single Protein Fe II Ligand Are Catalytically Active
Human Oxygenase Variants Employing a Single Protein Fe II Ligand Are Catalytically Active
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采用单一蛋白质 Fe II 配体的人类加氧酶变体具有催化活性
DOI：
10.1002/ange.202103711
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发表时间：
2021
影响因子：
--
通讯作者：
Brasnett A
中科院分区：
文献类型：
--
作者：
Brasnett A
天冬氨酸/天冬酰胺-β-羟化酶（AspH）是一种人2-酮戊二酸（2 OG）和FeII加氧酶，催化表皮生长因子样结构域（EGFD）的天冬氨酸/天冬酰胺残基的C3羟基化。不寻常的是，AspH采用两个组氨酸残基螯合FeII，而不是两个组氨酸和一个谷氨酸/天冬氨酸残基的典型三联体。我们报告的动力学，抑制，和晶体学研究有关人类AspH的变体，其中任何一个FII结合组氨酸残基取代丙氨酸。H725 A和特别是H679 A AspH变体都保留了基本的催化活性。晶体结构清楚地揭示了仅通过单个蛋白质组氨酸配体的金属连接。这些结果对2 OG加氧酶的功能分配和非蛋白质仿生催化剂的设计具有重要意义。
Aspartate/asparagine‐β‐hydroxylase (AspH) is a human 2‐oxoglutarate (2OG) and FeIIoxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor‐like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeIIrather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its FeIIbinding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal‐ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non‐protein biomimetic catalysts.