title: An unexpectedly efficient catalytic antibody operating by ping-pong and induced fit mechanisms.
abstract: A transition state analogue was used to produce a mouse antibody that catalyzes transesterification in water. The antibody behaves as a highly efficient catalyst with a covalent intermediate and the characteristic of induced fit. While some features of the catalytic pathway were programmed when the hapten was designed and reflect favorable substrate-antibody interactions, other features are a manifestation of the chemical potential of antibody diversity. The fact that antibodies recapitulate mechanisms and pathways previously thought to be a characteristic of highly evolved enzymes suggests that once an appropriate binding cavity is achieved, reaction pathways commensurate with the intrinsic chemical potential of proteins ensue.
authors.affiliation: Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: P
authors.initials: P
authors.lastname: Wirsching
authors.forename: J A
authors.initials: JA
authors.lastname: Ashley
authors.forename: S J
authors.initials: SJ
authors.lastname: Benkovic
authors.forename: K D
authors.initials: KD
authors.lastname: Janda
authors.forename: R A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000215:Acylation; D000438:Alcohols / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism; D004951:Esterification; D006241:Haptens; D007700:Kinetics; D051379:Mice; D014867:Water
chemical_list: D000438:Alcohols; D000911:Antibodies, Monoclonal; D004798:Enzymes; D006241:Haptens; D014867:Water