Accession Number : ADA266792


Title :   Analysis of Structure and Specific Functional Groups Involved in Acetylcholinesterase Catalysis and Inhibition


Descriptive Note : Rept. for 14 Jun 92-14 Dec 92,


Corporate Author : CALIFORNIA UNIV SAN DIEGO LA JOLLA DEPT OF PHARMACOLOGY


Personal Author(s) : Taylor, Palmer


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a266792.pdf


Report Date : 15 Dec 1992


Pagination or Media Count : 19


Abstract : The acetylcholinesterase genes from Torpedo, mouse and man and the butyrylcholinesterase gene from mouse have been expressed in mammalian and baculovirus based expression systems. The former system has enabled us to rapidly ascertain the kinetic properties and inhibitor specificity of recombinant DNA-derived, site-specific mutants and chimeras of the cholinesterases. The latter expression system has proven useful for large-scale production of cholinesterases for physical-chemical characterization. A large number of mutant enzymes and chimeras have been analyzed to define the residues responsible for substrate and inhibitor specificity. To this end we have assessed the role of charge in catalysis and binding, defined residues responsible for acyl pocket selectivity and for the specificity of acetyl- and butyrylcholinesterase selective inhibitors. In other studies, epitopes for molecular form specific and nonspecific monoclonal antibodies have been defined. Chemical modification studies with azidopropidium analogues have also identified peptides within the AChE structure contributing to the peripheral site.


Descriptors :   *CATALYSIS , *INHIBITORS , *ACETYLCHOLINESTERASE , MEMBRANES(BIOLOGY) , PRODUCTION , MODIFICATION , PEPTIDES , ENZYMES , SITES , ANIMALS , ACETYLCHOLINE , LABORATORY ANIMALS , ORGANOPHOSPHATES , AMINO ACIDS , RESIDUES , NUMBERS , GENETIC ENGINEERING , MONOCLONAL ANTIBODIES , KINETICS , GENES , STRUCTURES , DEOXYRIBONUCLEIC ACIDS , SCALE , ANTIBODIES , MOLECULAR STRUCTURE


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology


Distribution Statement : APPROVED FOR PUBLIC RELEASE