Bacterial phosphotriesterase

Ghanem E, Raushel EM (2005) Detoxification of organophosphate nerve agents by bacterial phosphotriesterase. Toxicol Appl Pharmacol 207(2, Supplement l) 459-47... 

Tsugawa, W., Nakamura, H., Sode, K., Ohuchi, S. (2000). Improvement of enantioselectivity of chiral organophosphate insecticide hydrolysis by bacterial phosphotriesterase. Appl. Biochem. Biotechnol. 84-6 311-17. 

Ghanem, E., Raushel, F.M. (2005). Detoxification of organo-phosphate nerve agents by bacterial phosphotriesterase. Toxicol. Appl. Pharmacol. 207 459-70. 

Selected Biological Aspects. - Phosphonate and phosphinic acids and their derivatives have been widely used in haptens. Examples additional to those already discussed in other sections include the phosphonic acid anion 363 which was an alternative to the preferred but synthetically inaccessible structure 364. The mechanism-based probe 365 has been synthesised and shown to modify a bacterial phosphotriesterase. This strategy for generating a probe is general and should allow the isolation of a host of unique catalysts. ... 

Figure 8 The hydrogen bond made between R254 and dimethyl substrates in the bacterial phosphotriesterase (PTE).

In contrast, alkynyl dialkyl phosphate esters, 78, are formed in good isolated yields by either the treatment of alkynyliodonium triflates with (R0)2P02Na or the reaction of terminal alkynes with [hydroxy(phosphoryloxy)iodo]benzene, 77 [Eq. (34)], or the sequential treatment of alkynylsilanes with PhIO Et20Bp3 followed by aqueous (R0)2P02Na [Eq. (35)) [61]. These new, alkynyliodonium-derived, acetylenic esters have potent biological activity [4] in particular, the alkynyl benzoates are protease inhibitors [62], whereas the alkynyl dialkylphos-phates, 78, are inhibitors of a bacterial phosphotriesterase [63]. 

Br3C H2SP03H2. In the enzymic hydrolysis of enantiomers of 0,S-dimethyl A -acetylphosphoramidothioate (acephate) with a bacterial phosphotriesterase, the (Sp) enantiomer is degraded lOOx faster than the (/ p) antipode. New observations have been reported on the ring-opening of epoxides in the system (56) by phosphorodithioate anions the compounds (57) and (58) are intermediates in the ultimate formation of (59),... 

Tsai P-C, Bigley A, Li Y, Ghanem E, Cadieux CL, Kasten SA, Reeves TE, Cerasoli DM, Raushel EM (2010) Stereoselective hydrolysis of organophosphate nerve agents by the bacterial phosphotriesterase. Biochemistry 49 7978-7987... 

An array of 16 enantiomeric pairs of chiral phosphate, phosphonate and phosphinate esters was used to establish the breadth of stereoselective discrimination inherent within the bacterial phosphotriesterase and 15 mutant enzymes. The results demonstrate that the catal5hic properties of the wide-type of phosphotriesterases can be exploited for the kinetic resolution of a wide-range of compounds and that the active site of this enzyme is remarkably amenable to structural perturbations via amino acid substitution. The first use of dialkyl phosphates as stereodirecting... 

Phosphotriesterase A bacterially produced enzyme that breaks down organophosphates like sarin. 

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