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.

[1]  N. Guex,et al.  SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling , 1997, Electrophoresis.

[2]  I. Smirnov,et al.  DNA hydrolyzing autoantibodies. , 1992, Science.

[3]  M. Arkin,et al.  Probing the importance of second sphere residues in an esterolytic antibody by phage display. , 1998, Journal of molecular biology.

[4]  M. Kussmann,et al.  Matrix-assisted laser desorption/ionization mass spectrometric peptide mapping of the neural cell adhesion protein neurolin purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis or acidic precipitation. , 1997, Journal of mass spectrometry : JMS.

[5]  G. Gololobov,et al.  Inhibition and labeling of enzymes and abzymes by phosphonate diesters , 2000, Applied biochemistry and biotechnology.

[6]  K. Courtney,et al.  A new and rapid colorimetric determination of acetylcholinesterase activity. , 1961, Biochemical pharmacology.

[7]  D. O'Shannessy,et al.  Detection of receptor-ligand interactions using surface plasmon resonance: model studies employing the HIV-1 gp120/CD4 interaction. , 1992, Analytical biochemistry.

[8]  S. Paul,et al.  Site-directed mutagenesis of proteolytic antibody light chain. , 1995, Journal of molecular biology.

[9]  A. Friboulet,et al.  Monoclonal anti-idiotypic antibodies as functional internal images of enzyme active sites: production of a catalytic antibody with a cholinesterase activity. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Peter G. Schultz,et al.  The Immunological Evolution of Catalysis , 1996, Science.

[11]  W. Jencks.  Catalysis in chemistry and enzymology , 1969 .

[12]  G. Siuzdak,et al.  Detection of a catalytic antibody species acylated at the active site by electrospray mass spectrometry. , 1995, Biochemistry.

[13]  D. Quinn,et al.  Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states , 1987 .

[14]  B. Golinelli‐Pimpaneau,et al.  Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  T. Scanlan,et al.  KINETIC AND MECHANISTIC CHARACTERIZATION OF AN EFFICIENT HYDROLYTIC ANTIBODY : EVIDENCE FOR THE FORMATION OF AN ACYL INTERMEDIATE , 1994 .

[16]  D. Hilvert,et al.  Hydrolytic antibodies: variations on a theme. , 1996, Chemistry & biology.

[17]  Alastair D G Lawson,et al.  Co‐expression of human protein disulphide isomerase (PDI) can increase the yield of an antibody Fab′ fragment expressed in Escherichia coli , 1996, FEBS letters.

[18]  M C Peitsch,et al.  The Swiss-3DImage collection and PDB-Browser on the World-Wide Web. , 1995, Trends in biochemical sciences.

[19]  P G Schultz,et al.  Selective chemical catalysis by an antibody. , 1986, Science.

[20]  A. Gabibov,et al.  DNA‐specific antiidiotypic antibodies in the sera of patients with autoimmune diseases , 1992, FEBS letters.

[21]  P Taylor,et al.  Three distinct domains in the cholinesterase molecule confer selectivity for acetyl- and butyrylcholinesterase inhibitors. , 1993, Biochemistry.

[22]  Dan S. Tawfik,et al.  Structural Convergence in the Active Sites of a Family of Catalytic Antibodies , 1997, Science.

[23]  J. Powers,et al.  Synthesis and kinetic studies of diphenyl 1-(N-peptidylamino)alkanephosphonate esters and their biotinylated derivatives as inhibitors of serine proteases and probes for lymphocyte granzymes. , 1997, Archives of biochemistry and biophysics.

[24]  T. Scanlan,et al.  Phage display of a catalytic antibody to optimize affinity for transition-state analog binding. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Lottspeich,et al.  Molecular characterization of fish neurolin: a growth-associated cell surface protein and member of the immunoglobulin superfamily in the fish retinotectal system with similarities to chick protein DM-GRASP/SC-1/BEN. , 1994, Differentiation; research in biological diversity.

[26]  G. Siuzdak,et al.  Dissection of an antibody-catalyzed reaction. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Glynn,et al.  Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase. , 1994, The Biochemical journal.

[28]  L M Amzel,et al.  Anti‐idiotypic antibodies: biological function and structural studies , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  H. Sambrook.  Molecular cloning : a laboratory manual. Cold Spring Harbor, NY , 1989 .

[30]  R J Fletterick,et al.  Crystal structure of a catalytic antibody with a serine protease active site. , 1994, Science.

[31]  A. Gnatt,et al.  Excavations into the active-site gorge of cholinesterases. , 1992, Trends in biochemical sciences.

[32]  G. Winter,et al.  Making antibodies by phage display technology. , 1994, Annual review of immunology.

[33]  A. Plückthun,et al.  Secretion and in vivo folding of the Fab fragment of the antibody McPC603 in Escherichia coli: influence of disulphides and cis-prolines. , 1991, Protein engineering.

[34]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[35]  E. Getzoff,et al.  Structural basis for amide hydrolysis catalyzed by the 43C9 antibody. , 1999, Journal of molecular biology.

[36]  F. Hamel,et al.  Cleavage of vasoactive intestinal peptide at multiple sites by autoantibodies. , 1991, The Journal of biological chemistry.

[37]  A. Friboulet,et al.  Functional mimicry: elicitation of a monoclonal antiidiotypic antibody hydrolizing β‐lactams , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.