Theoretical study of the mechanisms of substrate recognition by catalase
Theoretical study of the mechanisms of substrate recognition by catalase
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DOI：
10.1021/ja010512t
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发表时间：
2001-10-03
影响因子：
15
通讯作者：
Orozco, M
中科院分区：
文献类型：
--
作者：
Kalko, SG;Gelpí, JL;Orozco, M
利用经典分子相互作用势、经典分子动力学和活化分子动力学等多种理论方法对酿酒酵母过氧化氢酶的底物识别机理进行了研究。特别注意连接血红素基团和蛋白质外部的通道的存在。在这些计算的基础上，给出了该酶独特的催化性能以及与关键突变相关的酶效率变化的理论基础。根据我们的计算，水有望成为该酶的竞争性抑制剂，阻止过氧化氢进入活性部位。主通道是底物进入酶的首选途径，并与过氧化氢协同结合。然而，主通道对过氧化氢的总亲和力仅略大于对水的亲和力。检测到连接血红素基团与单体界面和NADP(H)结合部位的替代通道。这些次要渠道可能对产品发布很重要。
A variety of theoretical methods including classical molecular interaction potentials, classical molecular dynamics, and activated molecular dynamics have been used to analyze the substrate recognition mechanisms of peroxisomal catalase from Saccharomyces cerevisiae. Special attention is paid to the existence of channels connecting the heme group with the exterior of the protein. On the basis of these calculations a rationale is given for the unique catalytic properties of this enzyme, as well as for the change in enzyme efficiency related to key mutations. According to our calculations the water is expected to be a competitive inhibitor of the enzyme, blocking the access of hydrogen peroxide to the active site. The main channel is the preferred route for substrate access to the enzyme and shows a cooperative binding to hydrogen peroxide. However, the overall affinity of the main channel for H2O2 is only slightly larger than that for H2O. Alternative channels connecting the heme group with the monomer interface and the NADP(H) binding site are detected. These secondary channels might be important for product release.