Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis.
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1997
- Accession Number
- ADA329999
Entities
People
- Palmer W. Taylor
Organizations
- University of California, San Diego