Enzyme mimicry by the antiidiotypic antibody approach.
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 transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.
Kolesnikov
A V
AV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Mikluho-Maklaya Street, Moscow 117871, Russia.
Kozyr
A V
AV
Alexandrova
E S
ES
Koralewski
F
F
Demin
A V
AV
Titov
M I
MI
Avalle
B
B
Tramontano
A
A
Paul
S
S
Thomas
D
D
Gabibov
A G
AG
Friboulet
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017151:Antibodies, Catalytic / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D018716:Molecular Mimicry; D008969:Molecular Sequence Data
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D017931:DNA Primers