a Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16 - 18 , 04107 Leipzig , Germany.
b Translational Centre for Regenerative Medicine (TRM) Leipzig , University of Leipzig , Leipzig , Germany.
Expert Opin Ther Targets. 2016;20(4):447-61. doi: 10.1517/14728222.2016.1112378. Epub 2015 Nov 11.
Lactoperoxidase (LPO) belongs to the immunologically relevant mammalian heme peroxidases. The enzyme contributes in external secretions to the humoral immune defense against pathogens by oxidation of thiocyanate (SCN(-)) and iodide (I(-)). The generation of oxidized thiocyanate and/or iodine species is also important in numerous biotechnological applications of LPO.
In this review, we give an overview about the present knowledge of LPO concerning enzymatic structure, catalytic cycles and (pseudo-)halogenated species generated by the enzyme. Redox properties of LPO as well as kinetic aspects regarding the different enzymatic cycles are discussed in order to gain insights into the disturbance of the (pseudo-)halogenating enzyme activity under pathological conditions. Important structural features of LPO and crystallographic studies on the interaction and reaction of organic substrates with the enzyme are also summarized. A broad discussion is devoted to the binding and oxidation of substrates that either inhibit or promote LPO activity.
On the basis of these data, different strategies to further optimize LPO functions in humoral defense of mucous surfaces and biotechnological applications are discussed. In particular, hydrophobic organic substrates with a 3,4-dihydroxyphenyl partial structure considerably enhance the (pseudo-)halogenating activity of LPO. Their application provides, thus, a new strategy to enhance the anti-microbial activity of this enzyme.
乳过氧化物酶(LPO)属于具有免疫相关性的哺乳动物血红素过氧化物酶。该酶通过氧化硫氰酸盐(SCN(-))和碘化物(I(-)),为外部分泌液中的体液免疫防御贡献力量,以抵御病原体。氧化硫氰酸盐和/或碘化物的生成在 LPO 的许多生物技术应用中也很重要。
在这篇综述中,我们概述了 LPO 在酶的结构、催化循环和酶生成的(拟)卤化物种方面的现有知识。讨论了 LPO 的氧化还原性质以及与不同酶循环相关的动力学方面,以便深入了解病理条件下(拟)卤化酶活性的干扰。还总结了 LPO 的重要结构特征和关于有机底物与酶相互作用和反应的晶体学研究。广泛讨论了结合和氧化抑制或促进 LPO 活性的底物。
基于这些数据,讨论了进一步优化 LPO 在黏液表面体液防御和生物技术应用中功能的不同策略。特别地,具有 3,4-二羟基苯基部分结构的疏水性有机底物大大增强了 LPO 的(拟)卤化活性。因此,它们的应用为增强这种酶的抗微生物活性提供了一种新策略。