Open AccessIs strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?
Author(s) -
Ya-Jun Zheng,
Thomas C. Bruice
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.9.4285
Subject(s) - acceleration , mutant , papain , transition (genetics) , hydrogen bond , transition rate matrix , chemistry , state (computer science) , hydrogen , biophysics , chemical physics , physics , biology , biochemistry , computer science , molecule , mathematics , enzyme , algorithm , statistics , gene , classical mechanics , organic chemistry
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 × 105 .