AI Article Synopsis
- The biosynthetic pathway for the antibiotic fosfomycin involves unique enzymes, including hydroxypropylphosphonic acid epoxidase, which is a new type of non-haem mononuclear iron enzyme.
- The study presents six X-ray structures of this enzyme, providing insights into its various forms and how it interacts with substrates.
- Findings suggest that the enzyme can undergo a conformational change for substrate recognition and radical protection, and it can effectively bind iron for dioxygen without the typical co-substrate required by similar enzymes.
Article Abstract
The biosynthetic pathway of the clinically important antibiotic fosfomycin uses enzymes that catalyse reactions without precedent in biology. Among these is hydroxypropylphosphonic acid epoxidase, which represents a new subfamily of non-haem mononuclear iron enzymes. Here we present six X-ray structures of this enzyme: the apoenzyme at 2.0 A resolution; a native Fe(II)-bound form at 2.4 A resolution; a tris(hydroxymethyl)aminomethane-Co(II)-enzyme complex structure at 1.8 A resolution; a substrate-Co(II)-enzyme complex structure at 2.5 A resolution; and two substrate-Fe(II)-enzyme complexes at 2.1 and 2.3 A resolution. These structural data lead us to suggest how this enzyme is able to recognize and respond to its substrate with a conformational change that protects the radical-based intermediates formed during catalysis. Comparisons with other family members suggest why substrate binding is able to prime iron for dioxygen binding in the absence of alpha-ketoglutarate (a co-substrate required by many mononuclear iron enzymes), and how the unique epoxidation reaction of hydroxypropylphosphonic acid epoxidase may occur.
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