PMID: 12379355Oct 16, 2002

Pyridoxal-5'-phosphate-dependent catalytic antibodies

Journal of Immunological Methods
S GramatikovaPhilipp Christen

Abstract

Strategies for expanding the catalytic scope of antibodies include the incorporation of inorganic or organic cofactors into their binding sites. An obvious choice is pyridoxal-5'-phosphate (PLP), which is probably the most versatile organic cofactor of enzymes. Monoclonal antibodies against the hapten N(alpha)-(5'-phosphopyridoxyl)-L-lysine, a stable analog of the covalent coenzyme-substrate adducts were screened by a competition ELISA for binding of the PLP-amino acid Schiff base adduct. The Schiff base with its C4'-N alpha double bond is, in contrast to the hapten, a planar compound and is an obligatory intermediate in all PLP-dependent reactions of amino acids. This highly discriminating screening step eliminated all but 5 of 24 hapten-binding antibodies. The five remaining antibodies were tested for catalysis of the PLP-dependent alpha,beta-elimination reaction of beta-chloroalanine. Antibody 15A9 complied with this selection criterion and catalyzed in addition the cofactor-dependent transamination reaction of hydrophobic D-amino acids and oxo acids (k(cat)'=0.42 min(-1) with D-alanine at 25 degrees C). Homology modeling together with alanine scanning yielded a 3D model of Fab 15A9. The striking analogy between antibody 15A...Continue Reading

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Citations

Dec 28, 2005·Bioorganic & Medicinal Chemistry·Rachel L ClarkSimon P Mackay
Oct 17, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fang Wu, Heinz Gehring
Jun 23, 2006·The Journal of Biological Chemistry·Béatrice Golinelli-PimpaneauPhilipp Christen

Related Concepts

Catalysis
Haptens
Fab Immunoglobulins
Pyridoxal Phosphate
Antibodies, Catalytic
Tertiary Protein Structure

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