Thbacteriaphosphotriesterascatalyzes thhydrolysis oa widrangoorganophosphatinsecticides anchemicawarfaragents. Threactioproducts fothhydrolysis othinsecticidparaoxoarshowbelow.

Twstrains obacteria (Pseudomonas diminuta anFlavobacteriusp) werdiscoverei1972 that harboreplasmids containing a genthat expressea proteithat acteas aorganophosphathydrolase. Thenzymhas subsequently beeexpresseiE. colanpurifiethomogeneity. Thcatalytic constants fothhydrolysis oinsecticides such as paraoxoarextraordinary. Thk_cat ank_cat/Kvalues ar~10⁴ s^-1 an10⁸ M^-1 s^-1, respectively. Thsubstratspecificity is reasonably broad. Thphosphoryoxygecabreplacewith sulfuaneitheothtwethoxy-substituents cabreplacewith methyl, propyophenygroups. Thleaving groucaconsist oactivatephenols, alkythiols, ofluoride. Thability phenols, alkythiols, ofluoride. Thability othis enzymthydrolyzP-bonds has generatesignificant interest ithutilizatioothis proteifothcatalytic detoxificatioothchemicawarfaragents, sariansoman.

Ththredimensionax-ray structurophosphotriesterashas beesolveby thgrouoHazeHoldeat thUniversity oWisconsin. Thproteifolds as a(ab)₈-barrel. Thactivsitis centerearouna clusteosihistidinresidues. Thdivalent zinc ions fora binucleametacentewith a bridging hydroxide. Alsbridging thbinucleametacenteis a carbamatfunctionagrouformefrothpost-translationamodificatiooLysine-169 with a moleculoCO₂. Thoveralproteifolanthstructurothbinucleametacentearvery similatthenzymurease.

Thongoing projects with this fascinating proteisystearas follows.

• What is thchemicamechanisfophosphathydrolysis?
• What arthroles foeach othtwmetaions during binding ancatalysis?
• Cawusthis enzymas a templatfomoleculaevolutiostudies?
• Dithis enzymevolvovethpast 50 years tspecifically hydrolyzorganophosphatinsecticides?
• How cawmanipulatthstructurothactivsitby combinatoriagenetic by combinatoriagenetic anchemicameans tvastly improvthinherent ability thydrolyzorganophosphates andetoxify chemicawarfaragents?
• Cawutilizthwiltypenzymanmutant variants as a catalyst fothkinetic resolutioochiraorganophosphates?

Thfirst figurgraphically illustrates thoveralthree-dimensionafoloPTE. Thseconfigurshows threlationshibetweethtwmetaions ithbinucleametacentetogethewith thproteianbridging ligands.

Figur1	Figur2