Enantiospecificity of chloroperoxidase-catalyzed epoxidation: biased molecular dynamics study of a cis-β-methylstyrene/chloroperoxidase-compound I complex.
Enantiospecificity of chloroperoxidase-catalyzed epoxidation: biased molecular dynamics study of a cis-β-methylstyrene/chloroperoxidase-compound I complex.
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氯过氧化物酶催化环氧化的对映特异性：顺式β-甲基苯乙烯/氯过氧化物酶化合物I 复合物的偏向分子动力学研究。
DOI：
10.1016/j.bpj.2010.12.3729
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发表时间：
2011
影响因子：
3.4
通讯作者：
Chatfield,DavidC
中科院分区：
文献类型：
--
作者：
Morozov,AlexanderN;D'Cunha,Cassian;Alvarez,CarlosA;Chatfield,DavidC
对明确溶剂化的顺式-β-甲基苯乙烯/氯过氧化物酶-化合物 I 复合物进行分子动力学模拟，以确定环氧化的高对映特异性的原因。根据模拟，计算二维自由能势以区分可能发生 1S2R 和 1R2S 环氧化物产物反应的结合势阱。自由能势的收敛通过自适应偏置势加速。结合分析之后是 1S2R 和 1R2S 反应前体结构的分析，其中离开结合孔的底物将其反应性双键置于氧铁基血红素中心的空间位置附近。介绍了结合和反应前体构象的结构分析。我们发现 1)，Glu183 的变形对于 CPO 催化的环氧化很重要，正如之前根据实验结果假设的那样； 2)、结合自由能不提供导致各自环氧化物对映体的结构之间的显着差异； 3)，CPO 对顺式-β-甲基苯乙烯的对映专一性可能是由一组特定的残基引起的，这些残基在氧铁基血红素中心周围形成疏水核心。
Molecular dynamics simulations of an explicitly solvatedcis-β-methylstyrene/chloroperoxidase-Compound I complex are performed to determine the cause of the high enantiospecificity of epoxidation. From the simulations, a two-dimensional free energy potential is calculated to distinguish binding potential wells from which reaction to 1S2R and 1R2S epoxide products may occur. Convergence of the free energy potential is accelerated with an adaptive biasing potential. Analysis of binding is followed by analysis of 1S2R and 1R2S reaction precursor structures in which the substrate, having left the binding wells, places its reactive double bond in steric proximity to the oxyferryl heme center. Structural analysis of binding and reaction precursor conformations is presented. We find that 1), a distortion of Glu183is important for CPO-catalyzed epoxidation as was postulated previously based on experimental results; 2), the free energy of binding does not provide significant differentiation between structures leading to the respective epoxide enantiomers; and 3), CPO's enantiospecificity towardcis-β-methylstyrene is likely to be caused by a specific group of residues which form a hydrophobic core surrounding the oxyferryl heme center.