脱水
化学
催化作用
酶
羟脯氨酸
酶催化
立体化学
有机化学
药物化学
生物化学
作者
Li Jiang,Yiqian Yang,Lin Huang,Yan Zhang,Jingkun An,Yu Zheng,Yiwei Chen,Yanhong Liu,Jianhui Huang,Ee Lui Ang,Suwen Zhao,Huimin Zhao,Rong‐Zhen Liao,Yifeng Wei,Yan Zhang
标识
DOI:10.1021/acscatal.4c00216
摘要
The various isomers of hydroxyproline (HP) are widely distributed in nature, serving as key components of structural proteins, while their quaternized betaine derivatives function as osmoprotectants in many organisms. Aerobic bacteria degrade HPs through a variety of well-studied mechanisms. Recent studies show that certain anaerobic bacteria degrade HPs through distinct mechanisms, involving the O2-sensitive glycyl radical enzymes (GREs) t4L-HP dehydratase (HypD) and t4D-HP C–N lyase (HplG). Here, we report the discovery of two more GREs, N-methyl c4L-HP dehydratase (HpyG) and N-methyl c4D-HP dehydratase (HpzG), which catalyze radical-mediated dehydration of the two N-methyl-c4HP enantiomers, while also displaying significant activities toward their unmethylated substrates. Both GREs are associated with homologues of pyrroline-5-carboxylate reductase, which catalyze reduction of their products N-methyl-pyrroline-5-carboxylate to form N-methyl-proline. Crystal structures of HpyG and HpzG in complex with their substrates revealed active site architectures distinct from that of HypD and provided insights into the mechanism of enantioselective radical-mediated dehydration. Our research further expands the repertoire of diverse chemical mechanisms involved in the bacterial metabolism of highly prevalent HP isomers and derivatives in the anaerobic biosphere.
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