Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis
Abstract
During the project period we have initiated a completed studies in the following areas: (1) The crystal structure of a mouse acetylcholinesterase-fasciculin 2 complex has provided an essential template for structure-function studies; progress has been made in crystallizing acetylcholinesterasein the absence of fasciculin. (2) Studies of a series of enantiomeric organophosphates reacting with acetylcholinesterase have been completed; they have yielded vital information on their binding orientation in the ground and transition states. Residues on the enzyme governing enantiomer specificity and leaving group orientation have been defined through site-specific mutagenesis. (3) The interactions of fasciculin 2 with acetylcholinesterase have been studied by kinetic and site-specific mutagenesis methods. The fasciculin 2-acetylcholinesterase complex has enabled us to study entry of ligands to the active center gorge. (4) Studies in oxime reactivation of cholinesterase inhibited by the enantiomeric phosphates were undeataken using 2-PAM and HI-6 with wild-type and mutant acetylcholinesterases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1998
- Accession Number
- ADA354080
Entities
People
- Palmer W. Taylor
Organizations
- University of California, San Diego