人类亚硫酸盐氧化酶保守残基H304和R309突变的动力学结果表明存在机制复杂性。
Kinetic results for mutations of conserved residues H304 and R309 of human sulfite oxidase point to mechanistic complexities.
作者信息
Davis Amanda C, Johnson-Winters Kayunta, Arnold Anna R, Tollin Gordon, Enemark John H
机构信息
Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721-0041, USA.
出版信息
Metallomics. 2014 Sep;6(9):1664-70. doi: 10.1039/c4mt00099d.
Several point mutations in the gene of human sulfite oxidase (hSO) result in isolated sulfite oxidase deficiency, an inherited metabolic disorder. Three conserved residues (H304, R309, K322) are hydrogen bonded to the phosphate group of the molybdenum cofactor, and the R309H and K322R mutations are responsible for isolated sulfite oxidase deficiency. The kinetic effects of the K322R mutation have been previously reported (Rajapakshe et al., Chem. Biodiversity, 2012, 9, 1621-1634); here we investigate several mutants of H304 and R309 by steady-state kinetics, laser flash photolysis studies of intramolecular electron transfer (IET), and spectroelectrochemistry. An unexpected result is that all of the mutants show decreased rates of IET but increased steady-state rates of catalysis. However, in all cases the rate of IET is greater than the overall turnover rate, showing that IET is not the rate determining step for any of the mutations.
人类亚硫酸盐氧化酶（hSO）基因中的几个点突变会导致孤立性亚硫酸盐氧化酶缺乏症，这是一种遗传性代谢紊乱疾病。三个保守残基（H304、R309、K322）与钼辅因子的磷酸基团形成氢键，R309H和K322R突变是导致孤立性亚硫酸盐氧化酶缺乏症的原因。K322R突变的动力学效应此前已有报道（Rajapakshe等人，《化学生物多样性》，2012年，9卷，1621 - 1634页）；在此，我们通过稳态动力学、分子内电子转移（IET）的激光闪光光解研究以及光谱电化学方法研究了H304和R309的几个突变体。一个意外的结果是，所有突变体的IET速率均降低，但催化的稳态速率却增加。然而，在所有情况下，IET速率都大于总体周转速率，这表明IET不是任何一种突变的速率决定步骤。
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