Enzyme mimicry by the antiidiotypic antibody approach

Alexander V. Kolesnikov, Arina V. Kozyr, Elena S. Alexandrova, Frédéric Koralewski, Alexander V. Demin, Mikhail I. Titov, Bérangère Avalle, Alfonso Tramontano, Sudhir Paul, Daniel Thomas, Alexander G. Gabibov, Alain Friboulet

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The concept of 'internal image' of antiidiotypic antibodies has provided the basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was obtained as an antiidiotype to AE-2 mAb, a known inhibitor of acetylcholinesterase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody variable domain encodes the catalytic function, whereas neither part of the primary sequence of the Fab exhibited homology with the enzyme. The specific modification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dimensional modeling suggests the existence of a functional catalytic dyad Ser-His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised against transitionstate analog revealed structural similarity although both antibodies were elicited by two different approaches.

Original languageEnglish (US)
Pages (from-to)13526-13531
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number25
DOIs
StatePublished - Dec 5 2000
Externally publishedYes

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Catalytic Domain
Antibodies
Enzymes
Catalytic Antibodies
Immunoglobulin Fab Fragments
Cholinesterase Inhibitors
Immunoglobulin M
Anti-Idiotypic Antibodies
Light

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Kolesnikov, A. V., Kozyr, A. V., Alexandrova, E. S., Koralewski, F., Demin, A. V., Titov, M. I., ... Friboulet, A. (2000). Enzyme mimicry by the antiidiotypic antibody approach. Proceedings of the National Academy of Sciences of the United States of America, 97(25), 13526-13531. https://doi.org/10.1073/pnas.200360497

Enzyme mimicry by the antiidiotypic antibody approach. / Kolesnikov, Alexander V.; Kozyr, Arina V.; Alexandrova, Elena S.; Koralewski, Frédéric; Demin, Alexander V.; Titov, Mikhail I.; Avalle, Bérangère; Tramontano, Alfonso; Paul, Sudhir; Thomas, Daniel; Gabibov, Alexander G.; Friboulet, Alain.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 25, 05.12.2000, p. 13526-13531.

Research output: Contribution to journalArticle

Kolesnikov, AV, Kozyr, AV, Alexandrova, ES, Koralewski, F, Demin, AV, Titov, MI, Avalle, B, Tramontano, A, Paul, S, Thomas, D, Gabibov, AG & Friboulet, A 2000, 'Enzyme mimicry by the antiidiotypic antibody approach', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 25, pp. 13526-13531. https://doi.org/10.1073/pnas.200360497
Kolesnikov AV, Kozyr AV, Alexandrova ES, Koralewski F, Demin AV, Titov MI et al. Enzyme mimicry by the antiidiotypic antibody approach. Proceedings of the National Academy of Sciences of the United States of America. 2000 Dec 5;97(25):13526-13531. https://doi.org/10.1073/pnas.200360497
Kolesnikov, Alexander V. ; Kozyr, Arina V. ; Alexandrova, Elena S. ; Koralewski, Frédéric ; Demin, Alexander V. ; Titov, Mikhail I. ; Avalle, Bérangère ; Tramontano, Alfonso ; Paul, Sudhir ; Thomas, Daniel ; Gabibov, Alexander G. ; Friboulet, Alain. / Enzyme mimicry by the antiidiotypic antibody approach. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 25. pp. 13526-13531.
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