宽底物谱LarA消旋酶催化和底物特异性的结构基础

IF 13.1 1区 化学 Q1 CHEMISTRY, PHYSICAL
Santhosh Gatreddi, Julian Urdiain-Arraiza, Benoit Desguin*, Robert P. Hausinger* and Jian Hu*, 
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引用次数: 0

摘要

LarA家族由多种外消旋酶/外映酶组成,这些外消旋酶通过镍钳核苷酸(NPN)辅助因子将α-羟基酸的非对映体相互转化。由NPN辅助因子催化的隐性氧化还原反应使LarA酶成为各种应用的工程靶标。然而,LarA酶如何结合其天然底物并识别不同的α-羟基酸尚未阐明。在这里,我们报道了三种高分辨率结构的酶-底物复合物的广谱LarA酶来自苍白球(LarAIp)。底物结合模式揭示了氢化物供体和受体之间接近最佳的取向和距离,与更新的质子偶联氢化物转移机制一致。实验解决的结构,连同其他LarA酶的结构模型,导致鉴定残基/结构元件,关键参与与不同α-羟基酸的相互作用。总的来说,这项工作为LarA酶的催化和底物特异性提供了结构基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Structural Basis for the Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum

The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers of α-hydroxyacids by using a nickel-pincer nucleotide (NPN) cofactor. The hidden redox reaction catalyzed by the NPN cofactor makes LarA enzymes attractive engineering targets for various applications. However, how a LarA enzyme binds its natural substrate and recognizes different α-hydroxyacids has not been elucidated. Here, we report three high-resolution structures of the enzyme–substrate complexes of a broad-spectrum LarA enzyme from Isosphaera pallida (LarAIp). The substrate binding mode reveals a near-optimal orientation and distance between the hydride donor and acceptor, consistent with an updated proton-coupled hydride transfer mechanism. The experimentally solved structures, together with the structural models of other LarA enzymes, lead to the identification of the residues/structural elements that are critically involved in the interactions with different α-hydroxyacids. Collectively, this work provides a structural basis for the catalysis and substrate specificity of the LarA enzymes.

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来源期刊
ACS Catalysis
ACS Catalysis CHEMISTRY, PHYSICAL-
CiteScore
20.80
自引率
6.20%
发文量
1253
审稿时长
1.5 months
期刊介绍: ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.
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