4j1w | pdb_00004j1w

Crystal Structure of Fe(II)-HppE with alternative substrate (R)-1-HPP

spinqualitylabelsall models 4j1w, resolution 2.72Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4j1w is a 3 chain structure with sequence from "actinomyces_wedmorensis"_milard_and_burr_1926 "actinomyces wedmorensis" milard and burr 1926. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FE2, FFQ, GOL Related: 4j1x, 3scf, 3scg, 1zz8, 1zz7 Gene: fom4 ("Actinomyces wedmorensis" Milard and Burr 1926) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed (S)-2-hydroxypropylphosphonate ((S)-2-HPP) epoxidase (HppE) is a mononuclear non-haem-iron-dependent enzyme responsible for the final step in the biosynthesis of the clinically useful antibiotic fosfomycin. Enzymes of this class typically catalyse oxygenation reactions that proceed via the formation of substrate radical intermediates. By contrast, HppE catalyses an unusual dehydrogenation reaction while converting the secondary alcohol of (S)-2-HPP to the epoxide ring of fosfomycin. Here we show that HppE also catalyses a biologically unprecedented 1,2-phosphono migration with the alternative substrate (R)-1-HPP. This transformation probably involves an intermediary carbocation, based on observations with additional substrate analogues, such as (1R)-1-hydroxyl-2-aminopropylphosphonate, and model reactions for both radical- and carbocation-mediated migration. The ability of HppE to catalyse distinct reactions depending on the regio- and stereochemical properties of the substrate is given a structural basis using X-ray crystallography. These results provide compelling evidence for the formation of a substrate-derived cation intermediate in the catalytic cycle of a mononuclear non-haem-iron-dependent enzyme. The underlying chemistry of this unusual phosphono migration may represent a new paradigm for the in vivo construction of phosphonate-containing natural products that can be exploited for the preparation of new phosphonate derivatives. Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration reaction.,Chang WC, Dey M, Liu P, Mansoorabadi SO, Moon SJ, Zhao ZK, Drennan CL, Liu HW Nature. 2013 Apr 4;496(7443):114-8. doi: 10.1038/nature11998. PMID:23552950 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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