Comparison of thioethers and sulfoxides as axial ligands for N-acetylmicroperoxidase-8: implications for oxidation of methionine-80 in cytochrome c.
Comparison of thioethers and sulfoxides as axial ligands for N-acetylmicroperoxidase-8: implications for oxidation of methionine-80 in cytochrome c.
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硫醚和亚砜作为 N-乙酰微过氧化物酶 8 轴向配体的比较：对细胞色素 c 中蛋氨酸 80 氧化的影响。
DOI：
10.1021/ic034689v
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发表时间：
2003
影响因子：
4.6
通讯作者：
Benson,DavidR
中科院分区：
文献类型：
--
作者：
Lushington,GeraldH;Cowley,AaronB;Silchenko,Svetlana;Lukat-Rodgers,GudrunS;Rodgers,KentonR;Benson,DavidR
线粒体细胞染色质（cytc）中的蛋氨酸-80 （Met-80）可被活性氧氧化为相应的亚砜，这是一种具有潜在生物学意义的反应。作为研究Met-80氧化如何影响其与血红素铁相互作用的一种方法，我们研究了2-（甲基硫）乙醇（MTE）和二甲基亚砜（DMSO）的结合，分别是Met和Met（SO）侧链与亚铁和铁-乙酰基微过氧化物酶-8 （AcMP8）的模型。我们发现DMSO与Fe(III)-AcMP8的配位比MTE的配位强1.2 kcal/mol，尽管这两种配体都形成低自旋配合物。将Fe(III)-AcMP8的DMSO配合物的光谱数据与已发表的Met(SO)-80形式的铁细胞的光谱数据进行比较，我们可以得出Met(SO)-80在后者中不与铁协调的结论。DMSO对Fe(II)-AcMP8的配位比MTE强1.3 kcal/mol，而Met-80和Met(SO)-80在细胞中对Fe（II）的亲和力大致相等。这一结果表明细胞中血红素铁附近的空间环境不利于Met(SO)-80的配位。真空量子化学密度泛函理论计算证实了亚砜更大的亲和力，并表明通过氧的配位是非常有利的。共振拉曼光谱数据表明，溶液中氧的配位倾向保持不变。计算数据进一步表明，DMSO配合物的π回键具有显著的热稳定性，而铁-硫π回键对硫醚配合物的成键作用不显著。
Methionine-80 (Met-80) in mitochondrial cytochromec(cytc) can be oxidized to the corresponding sulfoxide by reactive oxygen species, a reaction of potential biological significance. As an approach to investigating how oxidation of Met-80 would influence its interactions with heme iron, we have examined binding of 2-(methylthio)ethanol (MTE) and dimethyl sulfoxide (DMSO), models for the side chains of Met and Met(SO), respectively, to ferrous and ferricN-acetylmicroperoxidase-8 (AcMP8). We find that DMSO coordinates 1.2 kcal/mol less strongly to Fe(III)-AcMP8 than does MTE, although both ligands form low-spin complexes. Comparison of spectroscopic data for the DMSO complex of Fe(III)-AcMP8 with published data for the Met(SO)-80 form of ferric cytcallows us to conclude that Met(SO)-80 does not coordinate to iron in the latter. DMSO coordinates to Fe(II)-AcMP8 1.3 kcal/mol more strongly than does MTE, whereas Met-80 and Met(SO)-80 are reported to have approximately equal affinity for Fe(II) in cytc. This result suggests that the steric environment near the heme iron in cytcdiscriminates against coordination of Met(SO)-80. Vacuum quantum chemical density functional theory calculations confirm the greater affinity of the sulfoxide and show that coordination via oxygen is strongly favored. Resonance Raman spectroscopic data indicate that the preference for coordination via oxygen is maintained in solution. The computational data further indicate that the DMSO complex derives significant enthalpic stabilization from π back-bonding but that iron to sulfur π back-bonding does not make a significant contribution to bonding in the thioether complex.
酶作用的化学动力学。
影响因子：
15
作者：
R. Alberty
通讯作者：
R. Alberty