Cho Kyung-Bin, Gauld James W
Contribution from the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, N9B 3P4 Canada.
J Am Chem Soc. 2004 Aug 25;126(33):10267-70. doi: 10.1021/ja049186i.
Density functional theory has been employed to model the binding of the intermediate substrate NHA, by nitric oxide synthases. In particular, the orientation and interactions of possibly catalytically important substrate hydrogens, with and without molecular oxygen bound to the active site heme group, are considered. Without O(2), three possible conformers have been found, with the energetically most favored structure being that in which both protons of the -NHOH moiety of NHA are directed toward the heme group. With oxygen bound, four different structures were found. The energetically lowest structure is again found to have both hydrogens of the -NHOH group pointing toward the heme group, thus forming hydrogen bonds between -NH- and the terminal oxygen, and between -OH and the inner oxygen of the heme-O(2) group. In addition, unprotonated structures of the substrate bound to the active site are considered and the proton affinity calculated.
密度泛函理论已被用于模拟一氧化氮合酶对中间底物NHA的结合。特别地，考虑了在活性位点血红素基团结合或未结合分子氧的情况下，可能具有催化重要性的底物氢的取向和相互作用。在没有O(2)的情况下，发现了三种可能的构象，能量上最有利的结构是NHA的-NHOH部分的两个质子都指向血红素基团的结构。在结合氧的情况下，发现了四种不同的结构。再次发现能量最低的结构是-NHOH基团的两个氢都指向血红素基团，从而在-NH-与末端氧之间以及-OH与血红素-O(2)基团的内氧之间形成氢键。此外，还考虑了与活性位点结合的底物的未质子化结构并计算了质子亲和力。
