DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: Origins of catalytic activity
Autor: | L. Scott Rodkey, Jon N. Rumbley, Alexander G. Gabibov, Oksana I. Makarevich, Dmitry V. Schourov, Gennady V. Gololobov, Catherine A. Rumbley, Edward W. Voss |
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Rok vydání: | 1997 |
Předmět: |
Models
Molecular Protein Conformation Immunology DNA Single-Stranded Antibodies Catalytic Crystallography X-Ray Catalysis Immunoglobulin Fab Fragments chemistry.chemical_compound Tumor Cells Cultured Animals A-DNA Molecular Biology Autoantibodies chemistry.chemical_classification Binding Sites biology Oligonucleotide Hydrolysis Autoantibody Antibodies Monoclonal Active site DNA Abzyme Amino acid Kinetics chemistry Biochemistry Immunoglobulin G Phosphodiester bond biology.protein |
Zdroj: | Molecular Immunology. 34:1083-1093 |
ISSN: | 0161-5890 |
DOI: | 10.1016/s0161-5890(97)00129-6 |
Popis: | Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg 2+ ions. DNA hydrolyzing activity was associated with BV 04-01 IgG, Fab, and SCA 04-01 proteins. Pronounced cleavage specificity for both ss and dsDNA was observed with efficient hydrolysis of the C-rich region of the oligonucleotide A 7 C 7 ATATAGCGCGT 7 as well as preference for cleavage within CG-rich regions of double-stranded DNA. Data on specificity of ssDNA hydrolysis and kinetic data obtained from wild-type SCA 04-01 and two SCA 04-01 mutants (L32Phe and L27dHis) were used to model the catalytically active antibody site utilizing the previously resolved X-ray structure of (dT) 3 liganded Fab 04-01. The resulting model suggested that BV 04-01 activates the target phosphodiester bond by induction of conformational strain. In addition, the antibody-DNA complex contained a potential Mg 2+ ion coordination site composed of the L32Tyr and L27dHis amino acid side chains and a DNA 3′-phosphodiester group. Induction of strain and metal coordination could be constituents of a mechanism by which this antibody catalyzed DNA hydrolysis. Sequence data for BV 04-01 V H and V L genes suggested that the proposed catalytic antibody active site was germ-line encoded. This observation suggests the hypothesis that catalytic activity might represent an important but unspecified function of some antibody molecules. |
Databáze: | OpenAIRE |
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