title: Is strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?
abstract: Nitriles are good inhibitors for the cysteine protease papain. However, a single amino acid mutation (Gln-19 --> Glu-19) in the active site makes the mutant enzyme a good catalyst for nitrile hydrolysis. A theoretical approach was used to examine the differential transition state stabilization in the papain mutant relative to the wild-type enzyme. Based on this study, we concluded that strong hydrogen bonding in the transition state is responsible for the observed rate enhancement of 4 x 10(5).
authors.affiliation: Department of Chemistry, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zheng
authors.forename: T C
authors.initials: TC
authors.lastname: Bruice
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008956:Models, Chemical; D009154:Mutation; D009570:Nitriles / Q000378:metabolism*; D010206:Papain / Q000235:genetics / Q000378:metabolism*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D010206:Papain