1AXT

IMMUNE VERSUS NATURAL SELECTION: ANTIBODY ALDOLASES WITH THE RATES OF NATURAL ENZYMES

Summary for 1AXT

• Entry DOI: 10.2210/pdb1axt/pdb
• Descriptor: IMMUNOGLOBULIN IGG2A (3 entities in total)
• Functional Keywords: immunoglobulin, antibody fab', catalyst, aldolase reaction
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane; Single-pass membrane protein (Potential): P01865
• Total number of polymer chains: 2
• Total formula weight: 47626.31

Authors

Heine, A.,Wilson, I.A. (deposition date: 1997-10-20, release date: 1998-10-28, Last modification date: 2024-11-20)

Primary citation

Barbas 3rd., C.F.,Heine, A.,Zhong, G.,Hoffmann, T.,Gramatikova, S.,Bjornestedt, R.,List, B.,Anderson, J.,Stura, E.A.,Wilson, I.A.,Lerner, R.A.
Immune versus natural selection: antibody aldolases with enzymic rates but broader scope.
Science, 278:2085-2092, 1997

PubMed Abstract: Structural and mechanistic studies show that when the selection criteria of the immune system are changed, catalytic antibodies that have the efficiency of natural enzymes evolve, but the catalytic antibodies are much more accepting of a wide range of substrates. The catalytic antibodies were prepared by reactive immunization, a process whereby the selection criteria of the immune system are changed from simple binding to chemical reactivity. This process yielded aldolase catalytic antibodies that approximated the rate acceleration of the natural enzyme used in glycolysis. Unlike the natural enzyme, however, the antibody aldolases catalyzed a variety of aldol reactions and decarboxylations. The crystal structure of one of these antibodies identified the reactive lysine residue that was selected in the immunization process. This lysine is deeply buried in a hydrophobic pocket at the base of the binding site, thereby accounting for its perturbed pKa.

PubMed: 9405338
DOI: 10.1126/science.278.5346.2085

Experimental method

X-RAY DIFFRACTION (2.15 Å)