儿茶酚-O-甲基转移酶的区域选择性赋予催化活性增强。
Regioselectivity of Catechol O-Methyltransferase Confers Enhancement of Catalytic Activity.
作者信息
Tsao Douglas, Liu Shubin, Dokholyan Nikolay V
机构信息
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599.
出版信息
Chem Phys Lett. 2011 Apr 20;506(4-6):135-138. doi: 10.1016/j.cplett.2011.03.048.
Abstract
Catechol O-methyltransferase (COMT) metabolizes catechol moieties by methylating a single hydroxyl group at the meta- or para- hydroxyl position. Hydrophobic amino acids near the active site of COMT influence the regioselectivity of this reaction. Our sequence analysis highlights their importance by showing that these residues are highly conserved throughout evolution. Reaction barriers calculated in the gas phase reveal a lower barrier during methylation at the meta- position, suggesting that the observed meta-regioselectivity of COMT can be attributed to the substrate itself, and that COMT has evolved residues to orient the substrate in a manner that increases the rate of catalysis.
摘要
儿茶酚-O-甲基转移酶（COMT）通过将间位或对位羟基上的单个羟基甲基化来代谢儿茶酚部分。COMT活性位点附近的疏水氨基酸会影响该反应的区域选择性。我们的序列分析表明，这些残基在整个进化过程中高度保守，从而突出了它们的重要性。在气相中计算的反应势垒显示，间位甲基化时的势垒较低，这表明观察到的COMT间位区域选择性可归因于底物本身，并且COMT已经进化出一些残基，以一种提高催化速率的方式使底物定向。
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