Comparison of the binding and reactivity of plant and mammalian peroxidases to indole derivatives by computational docking

Biochemistry
Henrik R HallingbäckRebecca C Wade

Abstract

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...Continue Reading

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Citations

Jul 18, 2008·Thyroid : Official Journal of the American Thyroid Association·Jack KesslerGeoff Eales
Jun 27, 2007·British Journal of Pharmacology·E MalleC Obinger
Jun 3, 2008·British Journal of Pharmacology·T LuH M Abu-Soud
Nov 23, 2011·Chemistry : a European Journal·Xiaojuan YangDihua Shangguan
Feb 19, 2008·Free Radical Biology & Medicine·Semira GalijasevicHusam M Abu-Soud
Jul 26, 2013·Journal of Lipid Research·Hao ZhangKirkwood A Pritchard
Jun 1, 2011·Molecular Informatics·Alberto MalvezziAntonia T-do Amaral
Jun 13, 2018·Journal of Clinical Biochemistry and Nutrition·Yoji Kato, Naoko Suga
Oct 1, 2010·Acta Neuropsychiatrica·Piotr GałeckiJanusz Szemraj
May 5, 2021·Journal of Medicinal Chemistry·Cuihua WangJohn W Chen
Jul 26, 2021·Journal of Inorganic Biochemistry·Olivia G CampHusam M Abu-Soud

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