Ballut Lionel, Violot Sébastien, Kumar Sanjeev, Aghajari Nushin, Balaram Hemalatha
Molecular Microbiology and Structural Biochemistry, CNRS, University of Lyon1, UMR5086, 7 Passage du Vercors, CEDEX 07, F-69367 Lyon, France.
Trivedi School of Biosciences, Ashoka University, Rajiv Gandhi Education City, Sonipat 131029, Haryana, India.
Biomolecules. 2023 Sep 12;13(9):1379. doi: 10.3390/biom13091379.
Glutamine amidotransferases (GATs) catalyze the hydrolysis of glutamine and transfer the generated ammonia to diverse metabolites. The two catalytic activities, glutaminolysis and the subsequent amination of the acceptor substrate, happen in two distinct catalytic pockets connected by a channel that facilitates the movement of ammonia. The pathway for the synthesis of guanosine monophosphate (GMP) from xanthosine monophosphate (XMP) is enabled by the GAT GMP synthetase (GMPS). In most available crystal structures of GATs, the ammonia channel is evident in their native state or upon ligand binding, providing molecular details of the conduit. In addition, conformational changes that enable the coordination of the two catalytic chemistries are also informed by the available structures. In contrast, despite the first structure of a GMPS being published in 1996, the understanding of catalysis in the acceptor domain and inter-domain crosstalk became possible only after the structure of a glutamine-bound mutant of GMPS was determined. In this review, we present the current status of our understanding of the molecular basis of catalysis in GMPS, becoming the first comprehensive assessment of the biochemical function of this intriguing enzyme.
谷氨酰胺酰胺转移酶（GATs）催化谷氨酰胺水解，并将产生的氨转移到各种代谢物上。谷氨酰胺分解以及随后受体底物的胺化这两种催化活性，发生在由一个促进氨移动的通道相连的两个不同催化口袋中。从黄苷单磷酸（XMP）合成鸟苷单磷酸（GMP）的途径由GAT GMP合成酶（GMPS）启动。在GATs的大多数现有晶体结构中，氨通道在其天然状态或配体结合后都很明显，提供了该通道的分子细节。此外，现有结构也揭示了使两种催化化学过程得以协调的构象变化。相比之下，尽管GMPS的首个结构于1996年发表，但只有在确定了GMPS谷氨酰胺结合突变体的结构后，才有可能了解受体结构域中的催化作用以及结构域间的相互作用。在这篇综述中，我们阐述了目前对GMPS催化作用分子基础的理解现状，这是对这种有趣酶的生化功能的首次全面评估。
