Search results for "Phosphoric Triester Hydrolases"

showing 3 items of 3 documents

Quantification of hydrolysis of toxic organophosphates and organophosphonates by diisopropyl fluorophosphatase from Loligo vulgaris by in situ Fourie…

2008

Abstract The enzyme diisopropyl fluorophosphatase (DFPase) from the squid Loligo vulgaris effectively catalyzes the hydrolysis of diisopropyl fluorophosphate (DFP) and a number of organophosphorus nerve agents, including sarin, soman, cyclosarin, and tabun. Up to now, the determination of kinetic data has been achieved by techniques such as pH-stat titration, ion-selective electrodes, and fluorogenic substrate analogs. We report a new assaying method using in situ Fourier transform infrared (FTIR) spectroscopy with attenuated total reflection (ATR) for the real-time determination of reaction rates. The method employs changes in the P–O–R stretching vibration of DFP and nerve agent substrate…

BiophysicsLoligoOrganophosphonatesInfrared spectroscopyCyclosarinBiochemistrychemistry.chemical_compoundSpectroscopy Fourier Transform InfraredmedicineOrganic chemistryAnimalsFourier transform infrared spectroscopyOrganophosphorus acid anhydrolaseMolecular BiologyDiisopropyl-fluorophosphataseTabunChromatographyHydrolysisOsmolar ConcentrationCell BiologyOrganophosphatesKineticsPhosphoric Triester HydrolaseschemistryAttenuated total reflectionDiisopropyl fluorophosphatemedicine.drugAnalytical biochemistry
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Reversed Enantioselectivity of Diisopropyl Fluorophosphatase against Organophosphorus Nerve Agents by Rational Design

2009

Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall en…

Models MolecularSarinStereochemistryRational designCyclosarinStereoisomerismGeneral ChemistryNervous SystemBiochemistryCatalysisKineticschemistry.chemical_compoundOrganophosphorus CompoundsPhosphoric Triester HydrolasesColloid and Surface ChemistrychemistrySomanHydrolasemedicineDiisopropyl fluorophosphateChemical Warfare AgentsCrystallizationDiisopropyl-fluorophosphatasemedicine.drugNerve agentJournal of the American Chemical Society
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Hydrolysis of Phosphotriesters: A Theoretical Analysis of the Enzymatic and Solution Mechanisms

2012

A theoretical study on the alkaline hydrolysis of paraoxon, one of the most popular organophosphorus pesticides, in aqueous solution and in the active site of Pseudomonas diminuta phosphotriesterase (PTE) is presented. Simulations by means of hybrid quantum mechanics/molecular mechanics (QM/MM) potentials show that the hydrolysis of paraoxon takes place through an A(N)D(N) or associative mechanism both in solution and in the active site of PTE. The results correctly reproduce the magnitude of the activation free energies and can be used to rationalize the observed kinetic isotope effects (KIEs) for the hydrolysis of paraoxon in both media. Enzymatic hydrolysis of O,O-diethyl p-chlorophenyl …

StereochemistryReaction mechanismsMolecular dynamicsParaoxonCatalysisEnzyme catalysisHydrolysisComputational chemistryCatalytic DomainPseudomonasEnzymatic hydrolysismedicinebiologyParaoxonLigandChemistryHydrolysisOrganic ChemistryLeaving groupActive siteEnzyme catalysisGeneral ChemistryAssociative substitutionModels TheoreticalSolutionsZincPhosphoric Triester Hydrolasesbiology.proteinQuantum chemistrymedicine.drugChemistry - A European Journal
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