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Science 20 March 1998:
Vol. 279. no. 5358, pp. 1929 - 1933
DOI: 10.1126/science.279.5358.1929
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Reports

Immunological Origins of Binding and Catalysis in a Diels-Alderase Antibody

Floyd E. Romesberg, * Ben Spiller, * Peter G. Schultz, dagger Raymond C. Stevens dagger

The three-dimensional structure of an antibody (39-A11) that catalyzes a Diels-Alder reaction has been determined. The structure suggests that the antibody catalyzes this pericyclic reaction through a combination of packing and hydrogen-bonding interactions that control the relative geometries of the bound substrates and electronic distribution in the dienophile. A single somatic mutation, serine-91 of the light chain to valine, is largely responsible for the increase in affinity and catalytic activity of the affinity-matured antibody. Structural and functional studies of the germ-line precursor suggest that 39-A11 and related antibodies derive from a family of germ-line genes that have been selected throughout evolution for the ability of the encoded proteins to form a polyspecific combining site. Germ line-encoded antibodies of this type, which can rapidly evolve into high-affinity receptors for a broad range of structures, may help to expand the binding potential associated with the structural diversity of the primary antibody repertoire.

F. E. Romesberg and P. G. Schultz, Howard Hughes Medical Institute and the Department of Chemistry, University of California, Berkeley, CA 94720, USA, and Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
B. Spiller and R. C. Stevens, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, and the Department of Chemistry, University of California, Berkeley, CA 94720, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.

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