Catalytic antibody 1F7 (chorismate mutase activity)
Mus musculus (house mouse)
Enzymes are protein molecules made by the body to carry out chemical reactions. Immunoglobulins are proteins made by the body in response to foreign intruders, antigens, and bind them tightly. This tells the body that there is a substance that does not belong into the body and has to be eliminated. As such these two classes of proteins seem to have little in common as far as their function is concerned, They do however share one feature: having very specific binding sites for the substances they deal with. This leads to the question: if antibodies have such specific recognition sites for particular compounds, could they not be persuaded to act like enzymes and catalyze chemical reactions? An American chemist, Richard Lerner, asked himself this question and as he tried to teach nature this new trick he found out that it works. And so catalytic antibodies were born. God did not make them, but Richard Lerner did. This antibody catalyzes the reaction of aromatic amino acids (Tyr and Phe) biosynthesis. Just giving a substrate or giving a product will not help. Antibodies will form that bind them and that will be it. Chemical reactions however proceed from substrate to product in intermediate step and providing an intermediate of the desired reaction does the trick.
The structure here shows the result of such an experiment, namely an antibody fragment, the part of an antibody that recognizes the antigen and a transition state analogue of a chemical reaction. The resulting catalytic antibody then carries out a function that is usually done by a known enzyme. Although the antibody here is not as efficient as the enzyme in doing this, it does catalyze the same reaction despite having a completely different overall structure.
Protein Data Bank (PDB)
Haynes, M.R. Stura, E.A. Hilvert, D. Wilson, I.A.; "Routes to catalysis: structure of a catalytic antibody and comparison with its natural counterpart."; Science; (1994) 263:646-652 PubMed:8303271.
author: Arno Paehler