Diversity in Hapten Recognition: Structural Study of an Anti-cocaine Antibody M82G2

• Published in: Journal of crystal growth Vol. 349; no. 3; pp. 570 - 582
• Main Authors: Pozharski, Edwin, Moulin, Aaron, Hewagama, Anura, Shanafelt, Armen B., Petsko, Gregory A., Ringe, Dagmar
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 10.06.2005
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Sequence; Animals; ANTIBODIES; antibody engineering; antibody structure; COCAINE; Cocaine - analysis; Cocaine - blood; Cocaine - immunology; CRYSTAL GROWTH; Hydrogen Bonding; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - genetics; Immunoglobulin Fab Fragments - immunology; immunotherapy; Ligands; Mice; Molecular Sequence Data; national synchrotron light source; Protein Binding - immunology; Protein Structure, Tertiary; protein–ligand interaction; Static Electricity; Structural Homology, Protein; antibody engineering; CDR; cocaine; antibody structure; protein–ligand interaction; immunotherapy
• ISSN: 0022-2836; 0022-0248; 1089-8638; 1873-5002
• DOI: 10.1016/j.jmb.2005.03.080

Antibodies against cocaine and other drugs of abuse are the basis for diagnostic tests for the presence of those drugs in human serum. The 1.7 Å resolution crystal structure of the anti-cocaine monoclonal antibody M82G2 in complex with cocaine is presented. This structure determination was undertaken to establish the stereochemical features in the antibody binding site that confer specificity for cocaine, and as part of an ongoing project to understand the rules that govern molecular recognition. The cocaine-binding site can be characterized topologically as a narrow groove on the protein surface. The antibody utilizes water-mediated hydrogen bonding, and cation–π and stacking (π–π) interactions to provide specificity. Comparison with the previously published structure of the anti-cocaine antibody GNC92H2 shows that binding of a small ligand can be achieved in diverse ways, both in terms of a binding site structure/topology and protein–ligand interactions.