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首页> 外文期刊>Journal of Molecular Biology >Structural insights into the substrate specificity of (S)-ureidoglycolate amidohydrolase and its comparison with allantoate amidohydrolase
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Structural insights into the substrate specificity of (S)-ureidoglycolate amidohydrolase and its comparison with allantoate amidohydrolase

机译：（S）-脲基乙醇酸酰胺水解酶的底物特异性的结构见解及其与尿囊酸酰胺水解酶的比较

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In plants, the ureide pathway is a metabolic route that converts the ring nitrogen atoms of purine into ammonia via sequential enzymatic reactions, playing an important role in nitrogen recovery. In the final step of the pathway, (S)-ureidoglycolate amidohydrolase (UAH) catalyzes the conversion of (S)-ureidoglycolate into glyoxylate and releases two molecules of ammonia as by-products. UAH is homologous in structure and sequence with allantoate amidohydrolase (AAH), an upstream enzyme in the pathway with a similar function as that of an amidase but with a different substrate. Both enzymes exhibit strict substrate specificity and catalyze reactions in a concerted manner, resulting in purine degradation. Here, we report three crystal structures of Arabidopsis thaliana UAH (bound with substrate, reaction intermediate, and product) and a structure of Escherichia coli AAH complexed with allantoate. Structural analyses of UAH revealed a distinct binding mode for each ligand in a bimetal reaction center with the active site in a closed conformation. The ligand directly participates in the coordination shell of two metal ions and is stabilized by the surrounding residues. In contrast, AAH, which exhibits a substrate-binding site similar to that of UAH, requires a larger active site due to the additional ureido group in allantoate. Structural analyses and mutagenesis revealed that both enzymes undergo an open-to-closed conformational transition in response to ligand binding and that the active-site size and the interaction environment in UAH and AAH are determinants of the substrate specificities of these two structurally homologous enzymes.
机译：在植物中，脲离子途径是通过顺序的酶促反应将嘌呤的环氮原子转化为氨的代谢途径，在氮的回收中起重要作用。在该途径的最后一步，（S）-脲基乙醇酸酯酰胺水解酶（UAH）催化（S）-脲基乙醇酸酯转化为乙醛酸酯，并释放出两分子氨作为副产物。 UAH与尿囊酸酰胺水解酶（AAH）在结构和序列上是同源的，尿囊酸酰胺水解酶（AAH）是该途径中的上游酶，功能与酰胺酶类似，但底物不同。两种酶都表现出严格的底物特异性，并以协调的方式催化反应，导致嘌呤降解。在这里，我们报告拟南芥UAH的三种晶体结构（与底物，反应中间体和产物结合），以及与尿囊酸酯复合的大肠杆菌AAH的晶体结构。 UAH的结构分析表明，双金属反应中心中每个配体的独特结合方式均与活性位点呈封闭构型有关。配体直接参与两个金属离子的配位壳，并被周围的残基稳定。相反，表现出与UAH相似的底物结合位点的AAH，由于尿囊酸酯中有额外的脲基，因此需要更大的活性位点。结构分析和诱变表明，这两种酶都响应配体结合而经历了从开到关的构象转变，UAH和AAH中的活性位点大小和相互作用环境是这两种结构同源酶底物特异性的决定因素。

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