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首页> 外文期刊>Biochemistry >Comparison of the binding and reactivity of plant and mammalian peroxidases to indole derivatives by computational docking
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Comparison of the binding and reactivity of plant and mammalian peroxidases to indole derivatives by computational docking

机译：通过计算对接比较植物和哺乳动物过氧化物酶与吲哚衍生物的结合和反应性

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The oxidation of melatonin by the mammalian myeloperoxidase (MPO) provides protection against the damaging effects of reactive oxygen species. Indole derivatives, such as melatonin and serotonin, are also substrates of the plant horseradish peroxidase (HRP), but this enzyme exhibits remarkable differences from MPO in the specificity and reaction rates for these compounds. A structural understanding of the determinants of the reactivity of these enzymes to indole derivatives would greatly aid their exploitation for biosynthetic and drug design applications. Consequently, after validation of the docking procedure, we performed computational docking of melatonin and serotonin to structural models of the ferric and compound I and II (co I and co II, respectively) states of HRP and MPO. The substrates dock at the heme edge on the distal side, but with different orientations in the two proteins. The distal cavity is larger in MPO than in HRP; however, in MPO, the substrates make closer contacts with the heme involving ring stacking, whereas in HRP, no ring stacking is observed. The observed differences in substrate binding may contribute to the higher reaction rates and lower substrate specificity of MPO relative to those of HRP. The docking results, along with the previously measured heme-protein reduction potentials, suggest that the differentially lowered reaction rates of co II of HRP and MPO with respect to those of co I could stem from as yet undetermined conformational or electrostatic differences between the co I and co II states of MPO, which are absent in HRP.
机译：哺乳动物的髓过氧化物酶（MPO）对褪黑激素的氧化作用可防止活性氧的破坏。吲哚衍生物，例如褪黑激素和5-羟色胺，也是植物辣根过氧化物酶（HRP）的底物，但是这些酶在特异性和反应速率方面与MPO表现出显着差异。对这些酶与吲哚衍生物反应性的决定因素有结构上的理解将极大地帮助其用于生物合成和药物设计应用。因此，在验证对接程序后，我们将褪黑激素和5-羟色胺计算对接至HRP和MPO的铁和化合物I和II（分别为co I和co II）状态的结构模型。底物停靠在远端的血红素边缘，但是两种蛋白质的取向不同。 MPO远侧腔比HRP大;然而，在MPO中，底物与血红素紧密接触，涉及环堆叠，而在HRP中，未观察到环堆叠。相对于HRP，观察到的底物结合差异可能有助于MPO更高的反应速率和更低的底物特异性。对接结果以及先前测得的血红蛋白还原电位表明，HRP和MPO的co II相对于co I的反应速率差异降低可能是由于co I之间的构象或静电差异尚未确定和HRP中不存在的MPO的co II状态。

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