Accession Number : ADA329999

Title :   Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis.

Descriptive Note : Annual rept. 6 Mar 96-5 Mar 97,

Corporate Author : CALIFORNIA UNIV SAN DIEGO LA JOLLA

Personal Author(s) : Taylor, Palmer W.

PDF Url : ADA329999

Report Date : APR 1997

Pagination or Media Count : 80

Abstract : In the second year of the grant, we have made excellent progress in several arenas: 1) The crystal structure of a mouse acetylcholinesterase-fasciculin 2 complex has provided an essential template for structure-function studies. 2) Studies with a series of enantiomeric organophosphates have been completed; they have yielded vital information on their binding orientation in the ground and transition states. Residues governing enantiomer specificity and leaving group orientation have been defined. 3) Studies in oxime reactivation of cholinesterase inhibited by the enantiomeric phosphates show two faces of attack between the oxime and the conjugated phosphonate. 4) The interactions of fasciculin 2 with acetylcholinesterase have been studied by kinetic and site-specific mutagenesis methods. The fasciculin2-acetylcholinesterase complex has enabled us to study entry of ligands to the active center gorge.

Descriptors :   *ACETYLCHOLINESTERASE, *CHOLINESTERASE, *ORGANOPHOSPHATES, *OXIMES, ACTIVATION, CRYSTAL STRUCTURE, ORIENTATION(DIRECTION), MUTATIONS, IDENTIFICATION, LIGANDS, CATALYSIS, TRANSITIONS, KINETICS, INHIBITION, PHOSPHONATES, RESIDUES.

Subject Categories : Biochemistry
      Inorganic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE