Structural insights into the biotechnologically relevant reversible NADPH-oxidizing NiFe-hydrogenase from P. furiosus

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2025-06-25 DOI:10.1016/j.str.2025.05.017

Xiansha Xiao, Gerrit J. Schut, Xiang Feng, Patrick M. McTernan, Dominik K. Haja, William N. Lanzilotta, Michael W.W. Adams, Huilin Li

引用次数: 0

Abstract

The cytoplasmic hydrogenase I (SHI) from the hyperthermophilic archaeon Pyrococcus furiosus belongs to the group III hydrogenase family. SHI oxidizes NADPH rather than NADH to reduce protons and evolve hydrogen gas, and because of this property, coupled with its high thermal stability, the enzyme holds great potential for economical hydrogen production. Despite decades of efforts, the SHI structure has remained unknown. Here, we report the cryoelectron microscopic (cryo-EM) structures of the heterotetrameric SHI holoenzyme (αδβγ). SHI is a symmetric dimer of two individually functional heterotetramers. SHI-αδ resembles the standard [NiFe] hydrogenase, and SHI-βγ function as the NADPH oxidoreductase. SHI-β contains three [4Fe-4S] clusters that relay electrons from NADPH in SHI-γ to the catalytic [NiFe] cluster in SHI-αδ for H₂ production. These structures will guide the adaptation of this unique enzyme for biotechnological applications.

Abstract Image

查看原文本刊更多论文

从P. furiosus生物技术相关可逆nadph氧化nife -氢化酶的结构见解

嗜热古细菌furiococcus的胞质氢化酶I （SHI）属于III族氢化酶家族。SHI氧化NADPH而不是NADH来还原质子并产生氢气，由于这种性质，加上它的高热稳定性，这种酶在经济制氢方面具有很大的潜力。尽管几十年的努力，SHI的结构仍然是未知的。本文报道了异四聚体SHI全酶（αδβγ）的低温电镜（cryo-EM）结构。SHI是两个独立功能的异四聚体的对称二聚体。SHI-αδ类似于标准的[NiFe]氢化酶，SHI-βγ具有NADPH氧化还原酶的功能。SHI-β含有3个[4Fe-4S]簇，将电子从SHI-γ中的NADPH传递到SHI-αδ中的催化[NiFe]簇，以产生H2。这些结构将指导这种独特的酶适应生物技术应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.