Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme

被引：18

作者：

Backman, Lindsey R. F. ^{[1
]}

Huang, Yolanda Y. ^{[2
,5
]}

Andorfer, Mary C. ^{[3
]}

Gold, Brian ^{[1
,6
]}

Raines, Ronald T. ^{[1
]}

Balskus, Emily P. ^{[2
]}

Drennan, Catherine L. ^{[1
,3
,4
]}

机构：

[1] MIT, Dept Chem, Cambridge, MA 02139 USA

[2] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[3] MIT, Dept Biol, Cambridge, MA 02139 USA

[4] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[5] Lawrence Berkeley Natl Lab, Dept Environm Genom & Syst Biol, Berkeley, CA USA

[6] Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA

来源：

ELIFE | 2020年 / 9卷

基金：

美国国家卫生研究院; 加拿大自然科学与工程研究理事会; 美国国家科学基金会;

关键词：

PYRUVATE FORMATE-LYASE; HYDROGEN-ATOM; CLOSTRIDIUM; ABSTRACTION; CHOLINE; ORGANIZATION; CONVERSION; CATALYSIS; BINDING;

D O I：

10.7554/eLife.51420

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：23

共 56 条

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