An Efficient Antibody-Catalyzed Aminoacylation Reaction

Autor: Shirlee Yonkovich, John R. Jacobsen, James R. Prudent, Lynn Kochersperger, Peter G. Schultz
Rok vydání: 1992
Předmět:
Zdroj: Science. 256:365-367
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.256.5055.365
Popis: An antibody generated against a neutral phosphonate diester transition-state analog was found to catalyze the aminoacylation of the 3'-hydroxyl group of thymidine with an alanyl ester. A comparison of the apparent second-order rate constant of the antibody-catalyzed reaction [5.4 x 10(4) molar-1 minute-1 (M-1 min-1)] with that of the uncatalyzed reaction (2.6 x 10(-4) M-1 min-1) revealed this to be a remarkably efficient catalyst. Moreover, although the concentration of water (55 M) greatly exceeds that of the secondary alcohol, the antibody selectively catalyzes acyl transfer to thymidine. The antibody exhibits sequential binding, with Michaelis constants of 770 microM and 260 microM for acyl acceptor and donor, respectively, and a dissociation constant of 240 pM for hapten. This antibody-catalyzed reaction provides increased insight into the requirements for efficient aminoacylation catalysts and may represent a first step toward the generation of "aminoacyl transfer RNA synthetases" with novel specificities.
Databáze: OpenAIRE