Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE) , CONICET and Universidad de Buenos Aires , Buenos Aires 1053 , Argentina.
Inorg Chem. 2018 Jul 2;57(13):7591-7600. doi: 10.1021/acs.inorgchem.8b00478. Epub 2018 Jun 19.
The reaction of hydrogen sulfide (HS) with hemeproteins is a key physiological reaction; still, its mechanism and implications are not completely understood. In this work, we propose a combination of experimental and theoretical tools to shed light on the reaction in model system microperoxidase 11 (MP11-Fe) and myoglobin (Mb-Fe), from the estimation of the intrinsic binding constants of the species HS and hydrosulfide (HS), and the computational description of the overall binding process. Our results show that HS and HS are the main reactive species in Mb-Fe and MP11-Fe, respectively, and that the magnitude of their intrinsic binding constants are similar to most of the binding constants reported so far for hemeproteins systems and model compounds. However, while the binding of HS to Mb-Fe was negligible, the binding of HS to MP11-Fe was significant, providing a frame for a discriminated analysis of both species and revealing differential mechanistic aspects. A joint inspection of the kinetic data and the free energy profiles of the binding processes suggests that a dissociative mechanism with the release of a coordinated water molecule as rate limiting step is operative in the binding of HS to Mb-Fe and that the binding of HS is prevented in the access to the protein matrix. For the MP11-Fe case, where no access restrictions for the ligands are present, an associative component in the mechanism seems to be operative. Overall, the results suggest that if accessing the active site then both HS and HS are capable of binding a ferric heme moiety.
硫化氢 (HS) 与血红素蛋白的反应是一种关键的生理反应，但该反应的机制和影响尚不完全清楚。在这项工作中，我们提出了将实验和理论工具相结合的方法，旨在阐明模型体系微过氧化物酶 11（MP11-Fe）和肌红蛋白（Mb-Fe）中的反应。我们通过估算 HS 和氢硫化物（HS）的固有结合常数，并对整个结合过程进行计算描述，来研究该反应。我们的结果表明，HS 和 HS 分别是 Mb-Fe 和 MP11-Fe 中的主要反应性物质，并且它们的固有结合常数的大小与迄今为止报道的大多数血红素蛋白体系和模型化合物的结合常数相似。然而，虽然 HS 与 Mb-Fe 的结合可以忽略不计，但 HS 与 MP11-Fe 的结合是显著的，为两种物质的区分分析提供了框架，并揭示了不同的机制方面。对动力学数据和结合过程的自由能曲线的综合检查表明，在 HS 与 Mb-Fe 的结合中，存在一个离解机制，其中释放一个配位水分子是速率限制步骤，而 HS 的结合在进入蛋白质基质时受到阻碍。对于 MP11-Fe 而言，由于不存在配体进入蛋白质基质的限制，因此在机制中似乎存在缔合成分。总体而言，结果表明，如果 HS 能够进入活性位点，那么它就能够与三价铁血红素部分结合。
