São Carlos Institute of Chemistry, University of São Paulo, São Carlos, SP, P.O. Box 780, ZIP Code 13560-970, Brazil.
São Carlos Institute of Chemistry, University of São Paulo, São Carlos, SP, P.O. Box 780, ZIP Code 13560-970, Brazil.
Arch Biochem Biophys. 2019 Jan;661:87-96. doi: 10.1016/j.abb.2018.11.009. Epub 2018 Nov 14.
First described in yeast in 1932 by Christian & Warburg, the Old Yellow Enzyme (OYE) (EC 1.6.99.1) has aroused the interest of the scientific community regarding its high ability to catalyze stereoselective reactions of α/β-unsaturated carbonyl compounds with important industrial applications. In addition, the OYE family of proteins has been found in different organisms, such as plants, bacteria and protozoa, but not in mammals, which makes it an excellent candidate for a functional and molecular study aimed at more effective therapies with fewer undesirable side effects. Several OYE orthologues have been characterized; however, the real physiological role for most members of this family of proteins remains a mystery. In this paper, we present the structural studies of the OYE of Leishmania braziliensis. The findings are discussed in comparison with OYE of Trypanosoma cruzi, revealing some biophysical differences. The main differences are related to their chemical and thermal stabilities and behavior in solution. In addition, the L. braziliensis OYE shape is more elongated than that of the T. cruzi orthologue. Despite this, the active sites of these enzymes do not appear to have major differences, since their interactions with the substrate menadione occur with an affinity of the same order of magnitude, revealing that the binding sites in both proteins are essentially similar.
1932 年，Christian 和 Warburg 在酵母中首次描述了 Old Yellow Enzyme（OYE）（EC 1.6.99.1），其能够高立体选择性地催化 α/β-不饱和羰基化合物的反应，具有重要的工业应用价值，这引起了科学界的兴趣。此外，OYE 蛋白家族在不同的生物体中被发现，如植物、细菌和原生动物，但在哺乳动物中没有发现，这使其成为功能和分子研究的理想候选物，旨在实现更有效的治疗，同时减少不良副作用。已经对几个 OYE 同源物进行了表征；然而，该蛋白家族的大多数成员的真正生理作用仍然是一个谜。在本文中，我们介绍了巴西利什曼原虫 OYE 的结构研究。将研究结果与克氏锥虫 OYE 进行了比较，揭示了一些生物物理差异。主要差异与它们的化学和热稳定性以及在溶液中的行为有关。此外，巴西利什曼原虫 OYE 的形状比克氏锥虫的同源物更加细长。尽管如此，这些酶的活性位点似乎没有明显的差异，因为它们与底物亚甲萘醌的相互作用具有相同数量级的亲和力，这表明这两种蛋白的结合位点基本相似。
