1zz7 | pdb_00001zz7
Crystal Structure of FeII HppE in Complex with Substrate form 1
Structural highlights
FunctionHPPE_STRWE Non-heme-dependent dioxygenase that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonate into (1R,2S)-epoxypropylphosphonate, the final step in the biosynthesis of fosfomycin antibiotic.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme.,Higgins LJ, Yan F, Liu P, Liu HW, Drennan CL Nature. 2005 Oct 6;437(7060):838-44. Epub 2005 Jul 13. PMID:16015285[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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