title: Nonspecific medium effects versus specific group positioning in the antibody and albumin catalysis of the base-promoted ring-opening reactions of benzisoxazoles.
abstract: The mechanisms by which solvents, antibodies, and albumins influence the rates of base-catalyzed reactions of benzisoxazoles have been explored theoretically. New experimental data on substituent effects and rates of reactions in several solvents, in an antibody, and in an albumin are reported. Quantum mechanical calculations were carried out for the reactions in water and acetonitrile, and docking of the transition state into a homology model of antibody 34E4 and an X-ray structure of human serum albumin was accomplished. A microenvironment made up of catalytic polar groups (glutamate in antibody 34E4 and lysine in human serum albumin) surrounded by relatively nonpolar groups is present in both catalytic proteins.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA 90095-1569, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Hu
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D017151:Antibodies, Catalytic / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002384:Catalysis; D007555:Isoxazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D017151:Antibodies, Catalytic; D007555:Isoxazoles; D012709:Serum Albumin