A structure-function study of a catalytic antiidiotypic antibody to the human erythrocyte acetyl cholinesterase

E. S. Aleksandrova, F. Koralevski, M. I. Titov, A. V. Demin, A. V. Kozyr', A. V. Kolesnikov, A. Tramontano, S. Paul, D. Thomas, A. G. Gabibov, N. V. Gnuchev, A. Friboulet

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1 Scopus citations

Abstract

The catalytic monoclonal antibody 9A8 (MA 9A8), antiidiotypic to the antibody AE-2 (MA AE2) produced to the active site of acetyl cholinesterase from human erythrocytes, was subjected to a structure-function study. The specific binding of MA 9A8 to MA AE2 (K 2.26 × 109 M -1) was found by the method of surface plasmon resonance, and the functional activity of MA 9A8 was demonstrated. Unlike acetyl cholinesterase, this antibody specifically reacted with the irreversible phosphonate inhibitors of esterases. A peptide map of MA 9A8 was analyzed by MALDI mass spectrometry. The Ser99 residue of its heavy chain was shown to be within the active site of the catalytic antibody. A computer modeling of the MA 9A8 active site suggested the existence of a catalytic dyad formed by Ser99 and His35. A comparison of the tertiary structures of the MA 9A8 and the 17E8 monoclonal antibody, which also exhibited the esterase activity and was produced to the stable analogue of the reaction transition state, indicated a practically complete coincidence of the structures of their presumed active sites.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalRussian Journal of Bioorganic Chemistry
Volume28
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Abzymes of acetyl cholinesterase
  • Antiidiotypic antibodies
  • Phosphonates
  • Surface plasmon resonance

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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  • Cite this

    Aleksandrova, E. S., Koralevski, F., Titov, M. I., Demin, A. V., Kozyr', A. V., Kolesnikov, A. V., Tramontano, A., Paul, S., Thomas, D., Gabibov, A. G., Gnuchev, N. V., & Friboulet, A. (2002). A structure-function study of a catalytic antiidiotypic antibody to the human erythrocyte acetyl cholinesterase. Russian Journal of Bioorganic Chemistry, 28(2), 101-107. https://doi.org/10.1023/A:1015013306504