title: Mechanistic investigation of methylphosphonate synthase, a non-heme iron-dependent oxygenase.
abstract: Methylphosphonate synthase is a non-heme iron-dependent oxygenase that converts 2-hydroxyethylphosphonate (2-HEP) to methylphosphonate. On the basis of experiments with two enantiomers of a substrate analog, 2-hydroxypropylphosphonate, catalysis is proposed to commence with stereospecific abstraction of the pro-S hydrogen on C2 of the substrate. Experiments with isotopologues of 2-HEP indicate stereospecific hydrogen transfer of the pro-R hydrogen at C2 of the substrate to the methyl group of methylphosphonate. Kinetic studies with these substrate isotopologues reveal that neither hydrogen transfer is rate limiting under saturating substrate conditions. A mechanism is proposed that is consistent with the available data.
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Cooke
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Peck
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Evans
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D005583:Fourier Analysis; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010105:Oxygenases / Q000378:metabolism*
chemical_list: D007501:Iron; D010105:Oxygenases; C577763:methylphosphonate synthase, Nitrosopumilus maritimus; D006419:Heme Oxygenase (Decyclizing)