Sequence-specific peptide cleavage catalyzed by an antibody.
Monoclonal antibodies have been induced that are capable of catalyzing specific hydrolysis of the Gly-Phe bond of peptide substrates at neutral pH with a metal complex cofactor. The antibodies were produced by immunizing with a Co(III) triethylenetetramine (trien)-peptide hapten. These antibodies as a group are capable of binding trien complexes of not only Co(III) but also of numerous other metals. Six peptides were examined as possible substrates with the antibodies and various metal complexes. Two of these peptides were cleaved by several of the antibodies. One antibody was studied in detail, and cleavage was observed for the substrates with the trien complexes of Zn(II), Ga(III), Fe(III), In(III), Cu(II), Ni(II), Lu(III), Mg(II), or Mn(II) as cofactors. A turnover number of 6 x 10(-4) per second was observed for these substrates. These results demonstrate the feasibility of the use of cofactor-assisted catalysis in an antibody binding site to accomplish difficult chemical transformations.
Iverson
B L
BL
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Lerner
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000276:immunology; D001666:Binding Sites, Antibody; D002384:Catalysis; D055598:Chemical Phenomena; D002621:Chemistry; D003035:Cobalt / Q000276:immunology / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006241:Haptens / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007114:Immunization; D008670:Metals / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D014266:Trientine / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D006241:Haptens; D008670:Metals; D009842:Oligopeptides; D003035:Cobalt; D010649:Phenylalanine; D014266:Trientine; D005998:Glycine