3SCH

Co(II)-HppE with R-HPP

Summary for 3SCH

• Entry DOI: 10.2210/pdb3sch/pdb
• Related: 3SCF 3SCG
• Descriptor: Epoxidase, [(2R)-2-hydroxypropyl]phosphonic acid, COBALT (II) ION, ... (4 entities in total)
• Functional Keywords: cupin-fold, hydroxypropylphosphonic acid epoxidase, mononuclear non-heme iron, metal binding protein
• Biological source: Streptomyces wedmorensis
• Total number of polymer chains: 2
• Total formula weight: 43589.22

Authors

Drennan, C.L. (deposition date: 2011-06-07, release date: 2011-07-06, Last modification date: 2023-12-06)

Primary citation

Yun, D.,Dey, M.,Higgins, L.J.,Yan, F.,Liu, H.W.,Drennan, C.L.
Structural basis of regiospecificity of a mononuclear iron enzyme in antibiotic fosfomycin biosynthesis.
J.Am.Chem.Soc., 133:11262-11269, 2011

PubMed 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 resolution; R-HPP with active iron-containing enzyme (Fe(II)-HppE) at 3.0 Å resolution; and S-HPP-Fe(II)-HppE in complex with dioxygen mimic NO at 2.9 Å 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.

PubMed: 21682308
DOI: 10.1021/ja2025728

Experimental method

X-RAY DIFFRACTION (2.1 Å)