Nutt David R, Meuwly Markus
Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
Chemphyschem. 2007 Mar 12;8(4):527-36. doi: 10.1002/cphc.200600563.
The binding of NO to iron is involved in the biological function of many heme proteins. Contrary to ligands like CO and O(2), which only bind to ferrous (Fe(II)) iron, NO binds to both ferrous and ferric (Fe(III)) iron. In a particular protein, the natural oxidation state can therefore be expected to be tailored to the required function. Herein, we present an ab initio potential-energy surface for ferric iron interacting with NO. This potential-energy surface exhibits three minima corresponding to eta(1)-NO coordination (the global minimum), eta(1)-ON coordination and eta(2) coordination. This contrasts with the potential-energy surface for Fe(II)-NO, which exhibits only two minima (the eta(2) coordination mode for Fe(II) is a transition state, not a minimum). In addition, the binding energies of NO are substantially larger for Fe(III) than for Fe(II). We have performed molecular dynamics simulations for NO bound to ferric myoglobin (Mb(III)) and compare these with results obtained for Mb(II). Over the duration of our simulations (1.5 ns), all three binding modes are found to be stable at 200 K and transiently stable at 300 K, with eventual transformation to the eta(1)-NO global-minimum conformation. We discuss the implication of these results related to studies of rebinding processes in myoglobin.
一氧化氮（NO）与铁的结合参与了许多血红素蛋白的生物学功能。与一氧化碳（CO）和氧气（O₂）等仅与亚铁（Fe(II)）结合的配体不同，NO既能与亚铁结合，也能与铁离子（Fe(III)）结合。因此，在特定的蛋白质中，其天然氧化态有望根据所需功能进行调整。在此，我们展示了铁离子与NO相互作用的从头算势能面。该势能面呈现出三个最小值，分别对应于η¹-NO配位（全局最小值）、η¹-ON配位和η²配位。这与Fe(II)-NO的势能面形成对比，后者仅呈现出两个最小值（Fe(II)的η²配位模式是一个过渡态，而非最小值）。此外，NO与Fe(III)的结合能比与Fe(II)的结合能大得多。我们对与高铁肌红蛋白（Mb(III)）结合的NO进行了分子动力学模拟，并将这些结果与Mb(II)的模拟结果进行了比较。在我们的模拟过程中（1.5纳秒），发现在200 K时所有三种结合模式都是稳定的，在300 K时是短暂稳定的，最终会转变为η¹-NO全局最小构象。我们讨论了这些结果对于肌红蛋白中再结合过程研究的意义。
