title: Inactivation of organophosphorus nerve agents by the phosphotriesterase from Pseudomonas diminuta.
abstract: The phosphotriesterase from Pseudomonas diminuta was tested as a catalyst for the hydrolysis of phosphofluoridates. The purified enzyme has been shown to hydrolyze the phosphorus-fluorine bond of diisopropyl fluorophosphate, isopropyl methylphosphonofluoridate, and 1,2,2-trimethylpropylmethylphosphonofluoridate at pH 7.0, 25 degrees C, with turnover numbers of 41, 56, and 5 s-1, respectively. The enzymatic rate enhancement for the hydrolysis of sarin at pH 7.0 is 2.2 X 10(7). The turnover number for paraoxon hydrolysis is 2100 s-1. The enzyme does not hydrolyze methanesulfonyl fluoride, phenylmethylsulfonyl fluoride, or O-p-nitrophenyl phenylsulfonate nor do these compounds inactivate or inhibit the ability of the enzyme to hydrolyze diethyl p-nitrophenyl phosphate. The breadth of substrate utility and the efficiency of the hydrolytic reaction exceed the more limited abilities of other prokaryotic and eukaryotic enzymes that catalyze similar reactions. The substantial rate enhancement exhibited by this enzyme for the hydrolysis of a wide variety of organophosphorus nerve agents make this enzyme the prime candidate for the biological detoxification of insecticide and mammalian acetylcholinesterase inhibitors.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station 77843.
authors.forename: D P
authors.initials: DP
authors.lastname: Dumas
authors.forename: H D
authors.initials: HD
authors.lastname: Durst
authors.forename: W G
authors.initials: WG
authors.lastname: Landis
authors.forename: F M
authors.initials: FM
authors.lastname: Raushel
authors.forename: J R
authors.initials: JR
authors.lastname: Wild
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase; D006868:Hydrolysis; D007700:Kinetics; D009498:Neurotoxins / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011549:Pseudomonas / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D009498:Neurotoxins; D009943:Organophosphorus Compounds; D010744:Phosphoric Monoester Hydrolases; D043303:Aryldialkylphosphatase