Wu Sangwook, Liu Shubin, Davis Charles H, Stafford Darrel W, Pedersen Lee G
Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290.
Int J Quantum Chem. 2010 Dec;110(15):2744-2751. doi: 10.1002/qua.22740.
We investigate the post-translational generation of Gla (γ-carboxy glutamic acid) from Glu (glutamic acid) by vitamin K carboxylase (VKC) in solvent. VKC is thought to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form, which then reacts with CO(2) to generate an essential ingredient in blood coagulation, γ-carboxyglutamic acid (Gla). The generation of Gla from Glu is found to be exergenic (-15 kcal/mol) in aqueous solution with the SM6 method. We also produced the free energy profile for this model biochemical process with other solvent methods (polarizable continuum model, dielectric polarizable continuum model) and different dielectric constants. The biological implications are discussed.
我们研究了溶剂中维生素K羧化酶（VKC）催化谷氨酸（Glu）进行翻译后生成γ-羧基谷氨酸（Gla）的过程。VKC被认为在维生素K循环中将维生素K转化为醇盐-环氧化物形式，然后该形式与二氧化碳反应生成血液凝固中的一种关键成分——γ-羧基谷氨酸（Gla）。采用SM6方法发现在水溶液中Glu生成Gla的过程是放能的（-15千卡/摩尔）。我们还使用其他溶剂方法（极化连续介质模型、介电极化连续介质模型）和不同的介电常数生成了该模型生化过程的自由能剖面图，并讨论了其生物学意义。
