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Immunological origins of binding and catalysis in a Diels-Alderase antibody.
- Source :
-
Science (New York, N.Y.) [Science] 1998 Mar 20; Vol. 279 (5358), pp. 1929-33. - Publication Year :
- 1998
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Antibodies chemistry
Antibodies genetics
Antibodies immunology
Antibodies metabolism
Antibodies, Catalytic genetics
Antibodies, Catalytic immunology
Antibody Affinity
Antibody Specificity
Binding Sites
Binding Sites, Antibody
Catalysis
Chemistry, Organic
Cloning, Molecular
Crystallography, X-Ray
Evolution, Molecular
Germ-Line Mutation
Haptens immunology
Hydrogen Bonding
Immunoglobulin Fab Fragments immunology
Immunoglobulin Fab Fragments metabolism
Models, Molecular
Molecular Sequence Data
Mutation
Organic Chemistry Phenomena
Protein Conformation
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Antibodies, Catalytic chemistry
Antibodies, Catalytic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0036-8075
- Volume :
- 279
- Issue :
- 5358
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 9506942
- Full Text :
- https://doi.org/10.1126/science.279.5358.1929