title: Structure-based rational design of a phosphotriesterase.
abstract: In silico substrate docking of both stereoisomers of the pesticide chlorfenvinphos (CVP) in the phosphotriesterase from Agrobacterium radiobacter identified two residues (F131 and W132) that prevent productive substrate binding and cause stereospecificity. A variant (W131H/F132A) was designed that exhibited ca. 480-fold and 8-fold increases in the rate of Z-CVP and E-CVP hydrolysis, respectively, eliminating stereospecificity.
authors.affiliation: CSIRO Entomology, Canberra, Australia.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Jackson
authors.forename: Kahli
authors.initials: K
authors.lastname: Weir
authors.forename: Anthony
authors.initials: A
authors.lastname: Herlt
authors.forename: Jeevan
authors.initials: J
authors.lastname: Khurana
authors.forename: Tara D
authors.initials: TD
authors.lastname: Sutherland
authors.forename: Irene
authors.initials: I
authors.lastname: Horne
authors.forename: Christopher
authors.initials: C
authors.lastname: Easton
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Russell
authors.forename: Colin
authors.initials: C
authors.lastname: Scott
authors.forename: John G
authors.initials: JG
authors.lastname: Oakeshott
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D020134:Catalytic Domain / Q000235:genetics*; D002709:Chlorfenvinphos / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D044345:Phosphoric Triester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012231:Rhizobium / Q000201:enzymology* / Q000235:genetics*; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D044345:Phosphoric Triester Hydrolases; D002709:Chlorfenvinphos