Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR), Singapore.
Biochem J. 2019 Jun 11;476(11):1605-1619. doi: 10.1042/BCJ20190206.
Taurine aminotransferases catalyze the first step in taurine catabolism in many taurine-degrading bacteria and play an important role in bacterial taurine metabolism in the mammalian gut. Here, we report the biochemical and structural characterization of a new taurine:2-oxoglutarate aminotransferase from the human gut bacterium (Toa). Biochemical assays revealed high specificity of Toa for 2-oxoglutarate as the amine acceptor. The crystal structure of Toa in complex with pyridoxal 5'-phosphate (PLP) and glutamate was determined at 2.7 Å resolution. The enzyme forms a homodimer, with each monomer exhibiting a typical type I PLP-enzyme fold and conserved PLP-coordinating residues interacting with the PLP molecule. Two glutamate molecules are bound in sites near the predicted active site and they may occupy a path for substrate entry and product release. Molecular docking reveals a role for active site residues Trp21 and Arg156, conserved in Toa enzymes studied to date, in interacting with the sulfonate group of taurine. Bioinformatics analysis shows that the close homologs of Toa are also present in other anaerobic gut bacteria.
牛磺酸氨基转移酶在许多牛磺酸降解细菌中催化牛磺酸分解的第一步，在哺乳动物肠道中的细菌牛磺酸代谢中发挥重要作用。在这里，我们报道了一种新的来自人类肠道细菌 （Toa） 的牛磺酸：2-氧代戊二酸氨基转移酶的生化和结构特征。生化测定表明 Toa 对 2-氧代戊二酸作为胺接受体具有很高的特异性。Toa 与吡哆醛 5'-磷酸（PLP）和谷氨酸复合物的晶体结构在 2.7 Å 分辨率下确定。该酶形成同源二聚体，每个单体表现出典型的 I 型 PLP-酶折叠，并且保守的 PLP 配位残基与 PLP 分子相互作用。两个谷氨酸分子结合在预测的活性位点附近的位置，它们可能占据底物进入和产物释放的途径。分子对接表明，活性位点残基 Trp21 和 Arg156（在迄今为止研究的 Toa 酶中保守）在与牛磺酸的磺酸基相互作用中起作用。生物信息学分析表明，Toa 的密切同源物也存在于其他厌氧肠道细菌中。
