Molecular dynamics study of the active site of methylamine dehydrogenase.
Molecular dynamics study of the active site of methylamine dehydrogenase.
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甲胺脱氢酶活性位点的分子动力学研究。
DOI：
10.1021/jp060715
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
J. Palma
中科院分区：
文献类型：
--
作者：
Gustavo Pierdominici;J. Echave;J. Palma
我们得到了甲胺脱氢酶(MADH)TTQ辅助因子的AMBER94力场参数。这种酶催化甲胺氧化生成甲醛和氨。在催化反应的速率确定步骤中，质子从底物的甲基转移到残基Asp76。我们使用新的参数对MADH进行了分子动力学模拟，以表征质子转移步骤之前活性中心的动力学。我们发现，Asp76中只有一个氧原子可以作为质子的受体。另一个氧通过强烈的氢键与Thr122相互作用。相反，由于底物的甲基的旋转，三个甲基氢原子交替地在要转移的位置上。质子的行进距离呈宽分布，峰值在1.0~1.1A之间，最短可达0.8A。施主与受主之间距离的起伏在50 cm(-1)处频率分量最大，但光谱在10~400 cm(-1)之间呈现丰富的结构。更重要的峰出现在250 cm(-1)以下。
We have obtained AMBER94 force-field parameters for the TTQ cofactor of the enzyme methylamine dehydrogenase (MADH). This enzyme catalyzes the oxidation of methylamine to produce formaldehyde and ammonia. In the rate-determining step of the catalyzed reaction, a proton is transferred from the methyl group of the substrate to residue Asp76. We used the new parameters to perform molecular dynamics simulations of MADH in order to characterize the dynamics of the active site prior to the proton-transfer step. We found that only one of the oxygen atoms of Asp76 can act as an acceptor of the proton. The other oxygen interacts with Thr122 via a strong hydrogen bond. In contrast, because of the rotation the methyl group of the substrate, the three methyl hydrogen atoms are alternately in position to be transferred. The distance that the proton has to travel presents a broad distribution with a peak between 1.0 and 1.1 A and reaches values as short as 0.8 A. The fluctuation of the distance between the donor and the acceptor has the largest frequency component at 50 cm(-1), but the spectrum presents a rich structure between 10 and 400 cm(-1). The more important peaks appear below 250 cm(-1).