Publication Date:
1992-04-17
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobsen, J R -- Prudent, J R -- Kochersperger, L -- Yonkovich, S -- Schultz, P G -- AI24695/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):365-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566082" target="_blank"〉PubMed〈/a〉
Keywords:
Acylation
;
Alanine/*metabolism
;
Amino Acyl-tRNA Synthetases/metabolism
;
Antibodies, Monoclonal/*metabolism
;
*Catalysis
;
Chromatography, High Pressure Liquid
;
Esterification
;
Haptens/immunology
;
Hemocyanin/immunology
;
Kinetics
;
Organophosphonates/*immunology
;
Serum Albumin, Bovine/immunology
;
Thymidine/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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