Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1.
An antibody generated to an alpha-keto amide containing hapten 1 catalyzes the cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the protein RNase T1. The antibody-catalyzed peptide isomerization reaction showed saturation kinetics for the cis-substrate, Suc-Ala-Ala-Pro-Phe-pNA, with a kcat/Km value of 883 s-1.M-1; the reaction was inhibited by the hapten analog 13 (Ki = 3. 0 +/- 0.4 microM). Refolding of denatured RNase T1 to its native conformation also was catalyzed by the antibody, with the antibody-catalyzed folding reaction inhibitable both by the hapten 1 and hapten analog 13. These results demonstrate that antibodies can catalyze conformational changes in protein structure, a transformation involved in many cellular processes.
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Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Hsieh-Wilson
L C
LC
Schultz
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PG
D017151:Antibodies, Catalytic / Q000378:metabolism*; D002384:Catalysis; D006241:Haptens / Q000276:immunology; D007536:Isomerism; D007659:Ketones / Q000276:immunology; D008956:Models, Chemical; D011392:Proline / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D006163:Ribonuclease T1 / Q000737:chemistry / Q000378:metabolism*
D017151:Antibodies, Catalytic; D006241:Haptens; D007659:Ketones; D011392:Proline; D006163:Ribonuclease T1