Department of Botany, University of Wisconsin-Madison, Madison, Wisconsin, USA.
The US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
J Biol Chem. 2022 Aug;298(8):102122. doi: 10.1016/j.jbc.2022.102122. Epub 2022 Jun 11.
Aminotransferases (ATs) are pyridoxal 5'-phosphate-dependent enzymes that catalyze the transamination reactions between amino acid donor and keto acid acceptor substrates. Modern AT enzymes constitute ∼2% of all classified enzymatic activities, play central roles in nitrogen metabolism, and generate multitude of primary and secondary metabolites. ATs likely diverged into four distinct AT classes before the appearance of the last universal common ancestor and further expanded to a large and diverse enzyme family. Although the AT family underwent an extensive functional specialization, many AT enzymes retained considerable substrate promiscuity and multifunctionality because of their inherent mechanistic, structural, and functional constraints. This review summarizes the evolutionary history, diverse metabolic roles, reaction mechanisms, and structure-function relationships of the AT family enzymes, with a special emphasis on their substrate promiscuity and multifunctionality. Comprehensive characterization of AT substrate specificity is still needed to reveal their true metabolic functions in interconnecting various branches of the nitrogen metabolic network in different organisms.
氨基转移酶（ATs）是依赖吡哆醛 5′-磷酸的酶，可催化氨基酸供体和酮酸受体底物之间的转氨基反应。现代 AT 酶构成所有分类酶活性的约 2%，在氮代谢中发挥核心作用，并产生多种初级和次级代谢物。ATs 可能在最后一个普遍共同祖先出现之前就已经分化为四个不同的 AT 类，并且进一步扩展为一个庞大而多样的酶家族。尽管 AT 家族经历了广泛的功能特化，但由于其固有的机制、结构和功能限制，许多 AT 酶仍然保留了相当大的底物通用性和多功能性。本综述总结了 AT 家族酶的进化历史、多样化的代谢作用、反应机制和结构-功能关系，特别强调了它们的底物通用性和多功能性。全面表征 AT 底物特异性仍然需要揭示它们在不同生物体的氮代谢网络的不同分支之间相互连接中的真实代谢功能。
