美国加州大学圣迭戈分校F. Akif Tezcan等研究人员合作揭示固氮酶对氧气的构象保护结构基础。2025年1月8日，《自然》杂志在线发表了这项成果。

要研究人员表示，还原氮气（N₂）所需的低还原电位使得基于金属的固氮催化剂容易受到氧气（O₂）的不可逆损伤。这种氧气敏感性对于固氮酶来说是一个主要难题，因为大部分固氮生物要么是严格需氧的，要么与呼吸氧气的生物紧密相关，以支持催化N₂还原的高能量需求。为了抵抗氧气对固氮酶的损害，固氮细菌使用氧气清除剂、利用隔离化或维持高呼吸速率以降低细胞内的氧气浓度。

最后一道防护线是通过“构象保护”机制提供的，在氧气应激下，一种[2Fe:2S]铁硫蛋白家族的蛋白质FeSII被激活，与固氮酶的组成蛋白形成一种耐氧的复合物。尽管已有一些前期的研究，但固氮酶的构象保护机制及FeSII激活的分子基础仍未完全理解。

研究人员通过冷冻电镜技术报告了Azotobacter vinelandii FeSII–固氮酶复合物的结构特征。研究揭示了一个核心复合物，由两种钼铁蛋白（MoFeP）、两种铁蛋白（FeP）和一个FeSII同源二聚体组成，它们聚合成延伸的纤维。在这个三蛋白复合物中，FeSII通过与MoFeP和FeP的广泛相互作用网络，定位它们的铁硫簇，使其处于催化失活但耐氧的状态。FeSII–固氮酶复合物的结构通过溶液研究得到了确认，进一步表明FeSII的激活涉及氧化引起的构象变化。

附：英文原文

Title: Structural basis for the conformational protection of nitrogenase from O2

Author: Narehood, Sarah M., Cook, Brian D., Srisantitham, Suppachai, Eng, Vanessa H., Shiau, Angela A., McGuire, Kelly L., Britt, R. David, Herzik, Mark A., Tezcan, F. Akif

Issue&Volume: 2025-01-08

Abstract: The low reduction potentials required for the reduction of dinitrogen (N2) render metal-based nitrogen-fixation catalysts vulnerable to irreversible damage by dioxygen (O2)1,2,3. Such O2 sensitivity represents a major conundrum for the enzyme nitrogenase, as a large fraction of nitrogen-fixing organisms are either obligate aerobes or closely associated with O2-respiring organisms to support the high energy demand of catalytic N2 reduction4. To counter O2 damage to nitrogenase, diazotrophs use O2 scavengers, exploit compartmentalization or maintain high respiration rates to minimize intracellular O2 concentrations4,5,6,7,8. A last line of damage control is provided by the ‘conformational protection’ mechanism9, in which a [2Fe:2S] ferredoxin-family protein termed FeSII (ref.10) is activated under O2 stress to form an O2-resistant complex with the nitrogenase component proteins11,12. Despite previous insights, the molecular basis for the conformational O2 protection of nitrogenase and the mechanism of FeSII activation are not understood. Here we report the structural characterization of the Azotobacter vinelandii FeSII–nitrogenase complex by cryo-electron microscopy. Our studies reveal a core complex consisting of two molybdenum–iron proteins (MoFePs), two iron proteins (FePs) and one FeSII homodimer, which polymerize into extended filaments. In this three-protein complex, FeSII mediates an extensive network of interactions with MoFeP and FeP to position their iron–sulphur clusters in catalytically inactive but O2-protected states. The architecture of the FeSII–nitrogenase complex is confirmed by solution studies, which further indicate that the activation of FeSII involves an oxidation-induced conformational change.

DOI: 10.1038/s41586-024-08311-1

Source: https://www.nature.com/articles/s41586-024-08311-1