DNA hydrolysis by monoclonal autoantibody BV 04-01

L. S. Rodkey, G. Gololobov, C. A. Rumbley, J. Rumbley, D. V. Schourov, O. I. Makarevich, A. G. Gabibov, E. W. Voss

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg2+. Catalysis was associated with BV 04-01 IgG, Fab, and single-chain-antibody (SCA) proteins. Cleavage of both ss and dsDNA was observed with efficient hydrolysis of the C-rich region of A7C7ATATAGCGCGT2, as well as a preference for cleaving within CG-rich regions of dsDNA. Data on specificity of ssDNA hydrolysis and kinetic data obtained from wild-type SCA, and two SCA mutants were used to model the catalytically active antibody site using the previously resolved X-ray structure of BV 04-01. The resulting model suggested that the target phosphodiester bond is activated by induction of conformational strain. In addition, the antibody-DNA complex contained a Mg2+ coordination site composed of the L32Tyr and L27dHis side chains and a DNA 3'-phosphodiester group. Induction of strain along with the metal coordination could be part of the mechanism by which this antibody catalyzes DNA hydrolysis. Sequence data for BV 04-01 V(H) and V(L) genes suggested that the proposed catalytic- antibody active site was germline-encoded. This observation suggests that catalytic activity might represent an important - rarely examined - function for some antibody molecules.

Original languageEnglish (US)
Pages (from-to)95-105
Number of pages11
JournalApplied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology
Volume83
Issue number1-3
StatePublished - Jun 19 2000

Keywords

  • Abzyme
  • Autoantibody
  • Catalysis

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    Rodkey, L. S., Gololobov, G., Rumbley, C. A., Rumbley, J., Schourov, D. V., Makarevich, O. I., Gabibov, A. G., & Voss, E. W. (2000). DNA hydrolysis by monoclonal autoantibody BV 04-01. Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology, 83(1-3), 95-105.