Hydrogenases are enzymes that catalyze the reversible reaction, \(\text{H}_{2} \rightleftharpoons 2\text{H}^{ + } + 2\text{e}^{ - }\), that occurs at the transition metal cluster in the catalytic center (e.g., [NiFe]). The catalytic activity of most standard hydrogenases is degraded by O₂ under aerobic conditions (O₂-sensitivity). However, the standard hydrogenase from Citrobacter sp. S-77 (termed S77 hereafter) can recover the activity; this phenomenon is called O₂-tolerance. Contrarily, on the basis of the current classification of standard hydrogenases, the structural features of S77 appear to be O₂-sensitive. The structural difference considered for the explanation seems to be just a replacement of an amino acid residue from Ser (most O₂-sensitive standard hydrogenases) to Ala121 (S77). Nevertheless, this residue is spatially located far for the direct mechanical interaction with the relevant, functional metal cluster [4Fe–4S] (∼7 Å), which thus remains a mystery. In this study, we theoretically analyzed this problem and thereby provided an explanation regarding this experimental discrepancy.

中文翻译：

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[4Fe–4S]附近簇附近氨基酸残基置换对[NiFe]-加氢酶的耐氧性的动力学影响的理论分析

氢化酶是催化可逆反应的酶， \（\ text {H} _ {2} \ rightleftharpoons 2 \ text {H} ^ {+} + 2 \ text {e} ^ {-} \）发生在催化中心的过渡金属簇（例如[NiFe]）上。大多数标准氢化酶的催化活性在有氧条件下被O ₂降解（O ₂敏感性）。然而，柠檬酸杆菌属的标准氢化酶。S-77（以下称为S77）可以恢复活性。这种现象称为O ₂耐受性。相反，基于当前标准氢化酶的分类，S77的结构特征似乎是对O ₂敏感的。考虑用于解释的结构差异似乎只是Ser（大多数O ₂对Ala121敏感的标准氢化酶（S77）。尽管如此，该残渣在空间上的位置远不及与相关的功能性金属簇[4Fe–4S]（〜7Å）的直接机械相互作用，因此仍然是个谜。在这项研究中，我们从理论上分析了这个问题，从而提供了有关此实验差异的解释。