Tissue transglutaminase (tTG) is capable of binding and hydrolyzing GTP, as well as catalyzing an enzymatic transamidation reaction that crosslinks primary amines to glutamine residues. tTG adopts two vastly different conformations, depending on whether it is functioning as a GTP-binding protein or a crosslinking enzyme. It has been shown to have important roles in several different aspects of cancer progression, making it an attractive target for therapeutic intervention. Here, we highlight many of the major findings involving tTG since its discovery 60 years ago, and describe recent drug discovery efforts that target specific activities or conformations of this unique protein.

组织转谷氨酰胺酶 (tTG) 能够结合和水解 GTP，并催化将伯胺与谷氨酰胺残基交联的酶促转酰胺基反应。 tTG 采用两种截然不同的构象，具体取决于它是作为 GTP 结合蛋白还是交联酶发挥作用。它已被证明在癌症进展的几个不同方面发挥着重要作用，使其成为治疗干预的有吸引力的目标。在这里，我们重点介绍了自 60 年前发现 tTG 以来的许多主要发现，并描述了最近针对这种独特蛋白质的特定活性或构象的药物发现工作。