Catalysis of concerted reactions by antibodies: the Claisen rearrangement.
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.
Hilvert
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Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Carpenter
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Nared
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Auditor
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001643:Bridged Bicyclo Compounds / Q000276:immunology*; D001952:Bridged-Ring Compounds / Q000276:immunology*; D002384:Catalysis; D002826:Chorismate Mutase / Q000037:antagonists & inhibitors*; D002827:Chorismic Acid / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism*; D053138:Cyclohexenes; D007535:Isomerases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D013816:Thermodynamics
D000911:Antibodies, Monoclonal; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D003509:Cyclohexanecarboxylic Acids; D053138:Cyclohexenes; D007535:Isomerases; D002826:Chorismate Mutase; D002827:Chorismic Acid; C005550:prephenic acid