DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: Origins of catalytic activity

Gennady V. Gololobov, Catherine A. Rumbley, Jon N. Rumbley, Dmitry V. Schourov, Oksana I. Makarevich, Alexander G. Gabibov, Edward W. Voss, L. Scott Rodkey

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg2+ 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 A7C7ATATAGCGCGT7 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 Mg2+ 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.

Original languageEnglish (US)
Pages (from-to)1083-1093
Number of pages11
JournalMolecular Immunology
Volume34
Issue number15
DOIs
StatePublished - Oct 1 1997

Keywords

  • Abzyme
  • Autoantibody
  • Catalysis

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    Gololobov, G. V., Rumbley, C. A., Rumbley, J. N., Schourov, D. V., Makarevich, O. I., Gabibov, A. G., Voss, E. W., & Rodkey, L. S. (1997). DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: Origins of catalytic activity. Molecular Immunology, 34(15), 1083-1093. https://doi.org/10.1016/S0161-5890(97)00129-6