Is strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?
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).
Zheng
Y J
YJ
Department of Chemistry, University of California, Santa Barbara, CA 93106, USA.
Bruice
T C
TC
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*
D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D010206:Papain