1zzb

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Crystal Structure of CoII HppE in Complex with Substrate

File:1zzb.gif


1zzb, resolution 2.30Å

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OverviewOverview

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.

About this StructureAbout this Structure

1ZZB is a Single protein structure of sequence from Streptomyces wedmorensis with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

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

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