Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Am Chem Soc. 2011 Jul 27;133(29):11262-9. doi: 10.1021/ja2025728. Epub 2011 Jun 30.
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.
羟基丙膦酸环氧化酶（HppE）是一种不寻常的单核铁酶，它使用分子氧催化抗生素磷霉素生物合成中（S）-2-羟丙膦酸（S-HPP）的氧化环氧化。此外，该酶还将底物的 R-对映体（R-HPP）转化为 2-氧代丙膦酸。为了探究 HppE 区域选择性的机制，我们确定了三个 X 射线结构：与惰性含钴酶（Co(II)-HppE）结合的 R-HPP，分辨率为 2.1 Å；与活性含铁酶（Fe(II)-HppE）结合的 R-HPP，分辨率为 3.0 Å；以及与模拟物 NO 结合的 S-HPP-Fe(II)-HppE，分辨率为 2.9 Å。这些结构与先前确定的 S-HPP-HppE 结构一起，确定了铁上的分子氧结合位点，并巧妙地说明了 HppE 如何能够识别两种底物对映体以催化两种完全不同的反应。
