Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme
Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme
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DOI：
10.7554/elife.51420
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发表时间：
2020-03-17
期刊：
影响因子：
7.7
通讯作者：
Drennan, Catherine L.
中科院分区：
文献类型：
--
作者：
Backman, Lindsey R. F.;Huang, Yolanda Y.;Drennan, Catherine L.
甘氨酰自由基酶 (GRE) 超家族利用甘氨酰自由基辅助因子来催化各种厌氧微生物代谢途径中的困难化学反应。最近，发现一种GRE，反式-4-羟基-L-脯氨酸（Hyp）脱水酶（HypD），可以催化Hyp脱水为（S）-Delta（1）-吡咯啉-5-羧酸（P5C）。这种酶在人类肠道微生物组中含量丰富，也存在于重要的细菌病原体中。然而，我们对 HypD 如何发挥其不寻常的化学作用缺乏了解。在这里，我们解析了来自艰难梭菌的 HypD 的晶体结构，Hyp 结合在活性位点上。生化研究已经确定了关键催化残基，并深入了解了 Hyp 脱水的根本机制。
The glycyl radical enzyme (GRE) superfamily utilizes a glycyl radical cofactor to catalyze difficult chemical reactions in a variety of anaerobic microbial metabolic pathways. Recently, a GRE, trans-4-hydroxy-L-proline (Hyp) dehydratase (HypD), was discovered that catalyzes the dehydration of Hyp to (S)-Delta(1)-pyrroline-5-carboxylic acid (P5C). This enzyme is abundant in the human gut microbiome and also present in prominent bacterial pathogens. However, we lack an understanding of how HypD performs its unusual chemistry. Here, we have solved the crystal structure of HypD from the pathogen Clostridioides difficile with Hyp bound in the active site. Biochemical studies have led to the identification of key catalytic residues and have provided insight into the radical mechanism of Hyp dehydration.