Analysis of hapten binding and catalytic determinants in a family of catalytic antibodies

Journal of Molecular Biology
H D Ulrich, P G Schultz

Abstract

We report here the cloning and kinetic analysis of a family of catalytic antibodies raised against a common transition state (TS) analog hapten, which accelerate a unimolecular oxy-Cope rearrangement. Sequence analysis revealed close homologies among the heavy chains of the catalytically active members of this set of antibodies, which derive mainly from a single germline gene, whereas the light chains can be traced back to several different, but related germline genes. The requirements for hapten binding and catalytic activity were determined by the construction of hybrid antibodies. Characterization of the latter antibodies again indicates a strong conservation of binding site structure among the catalytically active clones. The heavy chain was found to be the determining factor for catalytic efficiency, while the light chain exerted a smaller modulating effect that depended on light chain gene usage and somatic mutations. Within the heavy chain, the catalytic activity of a clone, but not hapten binding affinity, depended on the sequence of the third complementarity determining region (CDR). No correlation between high affinity for the hapten and high rate enhancement was found in the oxy-Cope system, a result that stands in c...Continue Reading

References

Mar 1, 1991·Bio/technology·J W Jacobs
Aug 8, 1991·Nature·J Foote, C Milstein
Feb 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·I Sanz, J D Capra
Aug 5, 1988·Journal of Molecular Biology·G A RathbunP W Tucker
Apr 1, 1987·Immunological Reviews·C Berek, C Milstein
Dec 19, 1986·Science·S J PollackP G Schultz
Dec 5, 1985·Journal of Molecular Biology·C ChothiaM Karplus
Dec 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R G HawleyN Hozumi
Sep 27, 1983·Biochemistry·P A Bartlett, C K Marlowe
Sep 29, 1995·Science·P G Schultz, R A Lerner
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D S TawfikZ Eshhar
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·J GuoT S Scanlan
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·K D JandaR A Lerner
Jun 1, 1994·European Journal of Immunology·C RadaC Milstein
Sep 1, 1993·European Journal of Immunology·H S RothenfluhE J Steele
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·H D UlrichP G Schultz
Feb 23, 1996·Science·P A PattenP G Schultz
Apr 1, 1996·Acta Chemica Scandinavica·H D UlrichP G Schultz
Jun 13, 1997·Science·G J WedemayerR C Stevens
Jan 1, 1997·Immunogenetics·H D UlrichP G Schultz

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Citations

Apr 3, 2003·Chembiochem : a European Journal of Chemical Biology·Montserrat BarbanyArieh Warshel
Nov 26, 2009·Journal of Molecular Recognition : JMR·Junjie XuGuangjun Nie
Jan 13, 2006·The Journal of Physical Chemistry. a·Sergio MartíJuan Bertrán

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