1zzb
Crystal Structure of CoII HppE in Complex with Substrate
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. 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 Page seeded by OCA on Sat May 3 18:16:03 2008