Structural Basis of Regiospecificity of a Mononuclear Iron Enzyme in Antibiotic Fosfomycin Biosynthesis
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Drennan_jacs2025728.pdf
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Author(s)
Yun, Danny
Dey, Mishtu
Higgins, Luke J.
Yan, Feng
Liu, Hung-wen
Drennan, Catherine L
Date Issued
June 2011
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Yun, Danny et al. “Structural Basis of Regiospecificity of a Mononuclear Iron Enzyme in Antibiotic Fosfomycin Biosynthesis.” Journal of the American Chemical Society 133.29 (2011) : 11262-11269. Copyright © 2011 American Chemical Society
Version
Final published version
Abstract
Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that uses dioxygen to catalyze the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid (S-HPP) in the biosynthesis of the antibiotic fosfomycin. Additionally, the enzyme converts the R-enantiomer of the substrate (R-HPP) to 2-oxo-propylphosphonic acid. To probe the mechanism of HppE regiospecificity, we determined three X-ray structures: R-HPP with inert cobalt-containing enzyme (Co(II)–HppE) at 2.1 Å [angstrom] resolution; R-HPP with active iron-containing enzyme (Fe(II)–HppE) at 3.0 Å [angstrom] resolution; and S-HPP–Fe(II)–HppE in complex with dioxygen mimic NO at 2.9 Å [angstrom] resolution. These structures, along with previously determined structures of S-HPP–HppE, identify the dioxygen binding site on iron and elegantly illustrate how HppE is able to recognize both substrate enantiomers to catalyze two completely distinct reactions.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/ja2025728
