Structural highlights
Function[OPD_SPHSA] Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe bacterial phosphotriesterase has been utilized as a template for the evolution of improved enzymes for the catalytic decomposition of organophosphate nerve agents. A combinatorial library of active site mutants was constructed by randomizing residues His-254, His-257, and Leu-303. The collection of mutant proteins was screened for the ability to hydrolyze a chromogenic analogue of the most toxic stereoisomer of the chemical warfare agent, soman. The mutant H254G/H257W/L303T catalyzed the hydrolysis of the target substrate nearly 3 orders of magnitude faster than the wild-type enzyme. The X-ray crystal structure was solved in the presence and absence of diisopropyl methyl phosphonate. The mutant enzyme was ligated to an additional divalent cation at the active site that was displaced upon the binding of the substrate analogue inhibitor. These studies demonstrate that substantial changes in substrate specificity can be achieved by relatively minor changes to the primary amino acid sequence. Enhanced degradation of chemical warfare agents through molecular engineering of the phosphotriesterase active site.,Hill CM, Li WS, Thoden JB, Holden HM, Raushel FM J Am Chem Soc. 2003 Jul 30;125(30):8990-1. PMID:15369336[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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