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 language | English (US) |
|---|---|
| Pages (from-to) | 13526-13531 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 97 |
| Issue number | 25 |
| DOIs | |
| State | Published - Dec 5 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
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 journal › Article
}
TY - JOUR
T1 - Enzyme mimicry by the antiidiotypic antibody approach
AU - Kolesnikov, Alexander V.
AU - Kozyr, Arina V.
AU - Alexandrova, Elena S.
AU - Koralewski, Frédéric
AU - Demin, Alexander V.
AU - Titov, Mikhail I.
AU - Avalle, Bérangère
AU - Tramontano, Alfonso
AU - Paul, Sudhir
AU - Thomas, Daniel
AU - Gabibov, Alexander G.
AU - Friboulet, Alain
PY - 2000/12/5
Y1 - 2000/12/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12944288311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12944288311&partnerID=8YFLogxK
U2 - 10.1073/pnas.200360497
DO - 10.1073/pnas.200360497
M3 - Article
C2 - 11095704
AN - SCOPUS:12944288311
VL - 97
SP - 13526
EP - 13531
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 25
ER -