Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme
Name
elife-51420-v1.pdf
Description
Published version
Size
3.18 MB
Format
Adobe PDF
Checksum (MD5)
b865b3b758cb86184b4716d2c49fa913
Author(s)
Backman, Lindsey R.
Huang, Yolanda Y
Andorfer, Mary
Gold, Brian
Raines, Ronald T
Balskus, Emily P
Drennan, Catherine L
Drennan, Catherine L
Date Issued
March 2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Backman, Lindsey R. F. et al. "Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme." eLife 9 (March 2020): e51420 © 2020 Backman et al.
Version
Final published version
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)-D1-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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/elife.51420
