Open AccessCatalysis of concerted reactions by antibodies: the Claisen rearrangement.
Author(s) -
Donald Hilvert,
S. H. Carpenter,
Karen D. Nared,
Maria-Teresa M. Auditor
Publication year - 1988
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.85.14.4953
Subject(s) - chorismate mutase , claisen rearrangement , chemistry , enzyme kinetics , transition state analog , stereochemistry , catalysis , mutase , kinetics , pericyclic reaction , monoclonal antibody , enzyme , antibody , active site , biochemistry , biology , biosynthesis , physics , quantum mechanics , immunology
Monoclonal antibodies were prepared against a transition state analog inhibitor of chorismate mutase (EC 5.4.99.5). One of the antibodies catalyzes the rearrangement of chorismate to prephenate with rate accelerations of more than 2 orders of magnitude compared to the uncatalyzed reaction. Saturation kinetics were observed, and at 25 degrees C the values of kcat and Km were 1.2 X 10(-3) s-1 and 5.1 X 10(-5) M respectively. The transition state analog was shown to be a competitive inhibitor of the reaction with Ki equal to 0.6 microM. These results demonstrate the feasibility of using rationally designed immunogens to generate antibodies that catalyze concerted reactions.