Format

Send to

Choose Destination
Elife. 2020 Mar 17;9. pii: e51420. doi: 10.7554/eLife.51420.

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

Author information

1
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United States.
2
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.
3
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
4
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
#
Contributed equally

Abstract

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)-Δ1-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.

KEYWORDS:

C. difficile; E. coli; biochemistry; chemical biology; glycyl radical enzyme; gut microbiome; hydroxyproline; molecular biophysics; radical chemistry; structural biology

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center