Factors that distort the heme structure in Heme-Nitric Oxide/OXygen-Binding (H-NOX) protein domains. A theoretical study.
Factors that distort the heme structure in Heme-Nitric Oxide/OXygen-Binding (H-NOX) protein domains. A theoretical study.
复制标题
扭曲血红素一氧化氮/氧结合 (H-NOX) 蛋白结构域中血红素结构的因素。
DOI：
10.1016/j.jinorgbio.2012.09.011
复制
发表时间：
2013
影响因子：
3.9
通讯作者：
Watts,JohnD
中科院分区：
文献类型：
--
作者：
Liao,Meng-Sheng;Huang,Ming-Ju;Watts,JohnD
采用密度泛函理论和色散校正密度泛函理论研究了血红素-一氧化氮/氧结合（H-NOX）蛋白结构域中血红素结构的畸变因素。各种模型系统，包括血红素，血红素+周围的残基，血红素+周围的残基+额外的蛋白质环境进行了检查，后者的系统计算与量子力学/分子力学（QM/MM）的方法。计算扩展到肌红蛋白（Mb）蛋白质，其中血红素结构是相当平面的，在H-NOX相反。血红素的自然倾向是平面的。H-NOX中强烈的结构扭曲主要是由整个血红素分子（血红素环加上其外围取代基）与周围残基之间的分子间相互作用引起的，其中极性残基（Tyr 140、Pro 115、Mse 98）在扭曲血红素结构中发挥了主要作用。位于血红素平面同一侧的两个外围丙酸取代基也能使分子发生畸变，但这种因素引起的畸变并不显著。在Mb中，所考虑的周围残基都是非极性的，不会引起结构畸变。通过计算再现了不同蛋白质（H-NOX和Mb）中血红素大环的不同结构特征。色散校正是必要的，因为它改善了计算的结构。畸变的轴向配体的血红素的结合亲和力的影响也进行了检查。
DFT and dispersion-corrected DFT calculations were carried out to probe the factors that distort the heme structure in Heme-Nitric oxide/OXygen-binding (H-NOX) protein domains. Various model systems that include heme, heme+surrounding residues, and heme+surrounding residues+additional protein environment were examined; the latter system was calculated with a quantum mechanics/molecular mechanics (QM/MM) method. The computations were extended to a myoglobin (Mb) protein, in which the heme structure is quite planar, in contrast to that in H-NOX. The natural tendency of the heme is to be planar. The strong structural distortion in H-NOX is mainly brought about by the intermolecular interactions between the whole heme molecule (heme ring plus its peripheral substituents) and the surrounding residues, among which the polar residues (Tyr140, Pro115, Mse98) play major roles in distorting the heme structure. The two peripheral propionate substituents that are oriented on the same side of the heme plane can also make the molecule distort, but the distortion caused by this factor is not significant. In Mb, the surrounding residues considered are all nonpolar and do not cause a structural distortion. The different structural features of the heme macrocycle in the different proteins (H-NOX and Mb) are reproduced by the calculations. The dispersion correction is necessary, since it improves the calculated structures. The effects of the distortion on the binding affinity of the axial ligand to the heme were also examined.