Benjamin Spiller
Last active: 2/25/2021

Immunological origins of binding and catalysis in a Diels-Alderase antibody.

Romesberg FE, Spiller B, Schultz PG, Stevens RC
Science. 1998 279 (5358): 1929-33

PMID: 9506942 · DOI:10.1126/science.279.5358.1929

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.

MeSH Terms (22)

Amino Acid Sequence Antibodies Antibodies, Catalytic Antibody Affinity Antibody Specificity Binding Sites Binding Sites, Antibody Catalysis Chemistry, Organic Cloning, Molecular Crystallography, X-Ray Evolution, Molecular Germ-Line Mutation Haptens Hydrogen Bonding Immunoglobulin Fab Fragments Models, Molecular Molecular Sequence Data Mutation Organic Chemistry Phenomena Protein Conformation Recombinant Proteins

Connections (1)

This publication is referenced by other Labnodes entities: