Catalase evolved to concentrate H2O2 at its active site
Catalase evolved to concentrate H2O2 at its active site
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DOI：
10.1016/j.abb.2010.05.017
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发表时间：
2010-08-01
影响因子：
3.9
通讯作者：
Hansberg, Wilhelm
中科院分区：
文献类型：
--
作者：
Dominguez, Laura;Sosa-Peinado, Alejandro;Hansberg, Wilhelm
过氧化氢酶是一种同源四聚体酶，其血红素活性位点深埋在蛋白质中。它的唯一底物过氧化氢（H2 O2）通过一个45 A长的通道到达血红素。大亚基过氧化氢酶（而不是小亚基过氧化氢酶）具有中断主通道的环（门环）。两个通路通向一个门，该门打开通向血红素的通道的最后一部分;来自R相关亚基的门是相互连接的。使用粗糙脉孢菌过氧化氢酶-1四聚体在一盒水（48，600个分子）或6 M H2 O2中的分子动力学模拟，表明H2 O2分子的数量在蛋白质的表面以及通道的门和最后部分的入口处增加。H2 O2的增加是由于H2 O2驻留增加的氨基酸（主要是组氨酸、脯氨酸和带电残基）的流行和分布，这些氨基酸位于蛋白质表面和通往门的通道。在该部分的通道从血红素的门，周转率的水分子比H2 O2和增加的居住地点的水和H2 O2进行了测定。在H2 O2的存在下，从特定位点排除水分子表明了一种可能与水的竞争活性相抗衡的机制，从而使过氧化氢酶具有高动力学效率。(C)2010年爱思唯尔公司All rights reserved.
Catalase is a homo-tetrameric enzyme that has its heme active site deeply buried inside the protein. Its only substrate, hydrogen peroxide (H2O2), reaches the heme through a 45 A-long channel. Large-subunit catalases, but not small-subunit catalases, have a loop (gate loop) that interrupts the major channel. Two accesses lead to a gate that opens the final section of the channel to the heme; gates from the R-related subunits are interconnected. Using molecular dynamic simulations of the Neurospora crassa catalase-1 tetramer in a box of water (48,600 molecules) or 6 M H2O2, it is shown that the number of H2O2 molecules augments at the surface of the protein and in the accesses to the gate and the final section of the channel. Increase in H2O2 is due to the prevalence and distribution of amino acids that have an increased residency for H2O2 (mainly histidine, proline and charged residues), which are localized at the protein surface and the accesses to the gate. In the section of the channel from the heme to the gate, turnover rate of water molecules was faster than for H2O2 and increased residence sites for water and H2O2 were determined. In the presence of H2O2, the exclusion of water molecules from a specific site suggests a mechanism that could contend with the competing activity of water, allowing for catalase high kinetic efficiency. (C) 2010 Elsevier Inc. All rights reserved.