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

104 Scopus citations

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

ASJC Scopus subject areas

  • Genetics
  • General

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    Kolesnikov, A. V., Kozyr, A. V., Alexandrova, E. S., Koralewski, F., Demin, A. V., Titov, M. I., Avalle, B., Tramontano, A., Paul, S., Thomas, D., Gabibov, A. G., & 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