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Published March 1, 1993 | public
Journal Article

Anomalous kinetics in antibody-antigen interactions

Abstract

The kinetics of hapten binding have been studied for one of a series of 12 anti-dinitrophenyl antibodies (Leahy; et al. Proc. Natl. Acad. Sci. U.S.A. 1988 85, 3661-3665). The kinetic on rate is 100-fold less than the diffusion limited rate. Furthermore, the kinetic on rate shows an anomalous temperature dependence that indicates the presence of two or more conformations of the antibody. Proton NMR spectra of the H3,5 protons of tyrosine residues show a temperature dependence of the conformation of one Tyr residue which is found in the combining site. Computer modeling of the structure of this antibody reveals that a portion of the heavy chain D region forms a loop structure which may be capable of inhibiting the access of the hapten to the combining site. Molecular dynamics calculations indicate that this loop is found in a single conformation at 5 °C, but adopts multiple conformations at 45 °C.

Additional Information

© 1993 American Chemical Society. Received: October 1, 1992; In Final Form: January 6, 1993. We would like to thank M. Levitt (Department Cell Biology, Stanford University) for constructing a model of AN01. We would also like to thank D. Benjamin (Department Microbiology, University of Virginia) for use of his IRIS workstation and help with the molecular dynamics calculations. We would like to especially thank one of the reviewers for his suggestions on the molecular dynamics calculations. This work was supported by the Office of Naval Research Contract N00014-90-J-1407 (H.M.M.). T.P.T. was a recipient of a U.S. Department of Education GAANN fellowship.

Additional details

Created:
August 20, 2023
Modified:
October 17, 2023