Gcn5 serves as the defining member of the Gcn5-related N-acetyltransferase (GNAT) superfamily of proteins that display a common structural fold and catalytic mechanism involving the transfer of the acyl-group, primarily acetyl-, from CoA to an acceptor nucleophile. In the case of Gcn5, the target is the ε-amino group of lysine primarily on histones. Over the years, studies on Gcn5 structure-function have often formed the basis by which we understand the complex activities and regulation of the entire protein acetyltransferase family. It is now appreciated that protein acetylation occurs on thousands of proteins and can reversibly regulate the function of many cellular processes. In this review, we provide an overview of our fundamental understanding of catalysis, regulation of activity and substrate selection, and inhibitor development for this archetypal acetyltransferase.

Gcn5 是 Gcn5 相关 N-乙酰转移酶 (GNAT) 蛋白质超家族的定义成员，其显示出共同的结构折叠和催化机制，涉及将酰基（主要是乙酰基）从 CoA 转移到受体亲核体。在 Gcn5 的情况下，目标是主要在组蛋白上的赖氨酸的 ε-氨基。多年来，对 Gcn5 结构-功能的研究往往成为我们了解整个蛋白质乙酰转移酶家族复杂活动和调控的基础。现在人们认识到，蛋白质乙酰化发生在数千种蛋白质上，并且可以可逆地调节许多细胞过程的功能。在这篇综述中，我们概述了我们对催化、活性调节和底物选择的基本理解，