title: Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases.
abstract: The founding members of the HD-domain protein superfamily are phosphohydrolases, and newly discovered members are generally annotated as such. However, myo-inositol oxygenase (MIOX) exemplifies a second, very different function that has evolved within the common scaffold of this superfamily. A recently discovered HD protein, PhnZ, catalyzes conversion of 2-amino-1-hydroxyethylphosphonate to glycine and phosphate, culminating a bacterial pathway for the utilization of environmentally abundant 2-aminoethylphosphonate. Using Mössbauer and EPR spectroscopies, X-ray crystallography, and activity measurements, we show here that, like MIOX, PhnZ employs a mixed-valent Fe(II)/Fe(III) cofactor for the O2-dependent oxidative cleavage of its substrate. Phylogenetic analysis suggests that many more HD proteins may catalyze yet-unknown oxygenation reactions using this hitherto exceptional Fe(II)/Fe(III) cofactor. The results demonstrate that the catalytic repertoire of the HD superfamily extends well beyond phosphohydrolysis and suggest that the mechanism used by MIOX and PhnZ may be a common strategy for oxidative C-X bond cleavage.
authors.affiliation: Departments of Chemistry, and Biochemistry and Molecular Biology, and Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802.
authors.forename: Bigna
authors.initials: B
authors.lastname: Wörsdörfer
authors.forename: Mahesh
authors.initials: M
authors.lastname: Lingaraju
authors.forename: Neela H
authors.initials: NH
authors.lastname: Yennawar
authors.forename: Amie K
authors.initials: AK
authors.lastname: Boal
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bollinger
authors.forename: Maria-Eirini
authors.initials: ME
authors.lastname: Pandelia
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D050562:Inositol Oxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D063065:Organophosphonates / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D015204:Spectroscopy, Mossbauer
chemical_list: D063065:Organophosphonates; D050562:Inositol Oxygenase
keywords: C-H activation; PhnY; nonheme diiron enzymes; structural genomics; superoxo intermediate