Olivares-Illana Vanesa, Riveros-Rosas Hector, Cabrera Nallely, Tuena de Gómez-Puyou Marietta, Pérez-Montfort Ruy, Costas Miguel, Gómez-Puyou Armando
Laboratorio de Interacciones Biomoleculares y Cáncer. Instituto de Física, Universidad Autónoma de San Luis Potosí, SLP, 78290, México.
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México.
Proteins. 2017 Jul;85(7):1190-1211. doi: 10.1002/prot.25299. Epub 2017 Apr 27.
Triosephosphate isomerase (TIM) is a ubiquitous enzyme, which appeared early in evolution. TIM is responsible for obtaining net ATP from glycolysis and producing an extra pyruvate molecule for each glucose molecule, under aerobic and anaerobic conditions. It is placed in a metabolic crossroad that allows a quick balance of the triose phosphate aldolase produced by glycolysis, and is also linked to lipid metabolism through the alternation of glycerol-3-phosphate and the pentose cycle. TIM is one of the most studied enzymes with more than 199 structures deposited in the PDB. The interest for this enzyme stems from the fact that it is involved in glycolysis, but also in aging, human diseases and metabolism. TIM has been a target in the search for chemical compounds against infectious diseases and is a model to study catalytic features. Until February 2017, 62% of all residues of the protein have been studied by mutagenesis and/or using other approaches. Here, we present a detailed and comprehensive recompilation of the reported effects on TIM catalysis, stability, druggability and human disease produced by each of the amino acids studied, contributing to a better understanding of the properties of this fundamental protein. The information reviewed here shows that the role of the noncatalytic residues depend on their molecular context, the delicate balance between the short and long-range interactions in concerted action determining the properties of the protein. Each protein should be regarded as a unique entity that has evolved to be functional in the organism to which it belongs. Proteins 2017; 85:1190-1211. © 2017 Wiley Periodicals, Inc.
磷酸丙糖异构酶（TIM）是一种普遍存在的酶，在进化过程中出现得较早。TIM负责在有氧和无氧条件下从糖酵解中获取净ATP，并为每个葡萄糖分子产生一个额外的丙酮酸分子。它处于一个代谢十字路口，能使糖酵解产生的磷酸丙糖醛缩酶快速达到平衡，还通过3-磷酸甘油和戊糖循环的交替与脂质代谢相联系。TIM是研究最多的酶之一，蛋白质数据库（PDB）中存有199种以上的结构。对这种酶的兴趣源于它不仅参与糖酵解，还与衰老、人类疾病和代谢有关。TIM一直是寻找抗传染病化合物的靶点，也是研究催化特性的模型。截至2017年2月，该蛋白质所有残基的62%已通过诱变和/或其他方法进行了研究。在此，我们对所研究的每个氨基酸对TIM催化、稳定性、成药可能性和人类疾病产生的已报道效应进行了详细而全面的重新整理，有助于更好地理解这种基础蛋白质的特性。此处综述的信息表明，非催化残基的作用取决于其分子环境，协同作用中短程和长程相互作用之间的微妙平衡决定了蛋白质的特性。每种蛋白质都应被视为一个独特的实体，其进化目的是在所属生物体中发挥功能。《蛋白质》2017年；85:1190 - 1211。©2017威利期刊公司。
