2E27

Crystal structure of Fv fragment of anti-ciguatoxin antibody complexed with ABC-ring of ciguatoxin

Summary for 2E27

• Entry DOI: 10.2210/pdb2e27/pdb
• Descriptor: anti-ciguatoxin antibody, light chain, anti-ciguatoxin antibody, heavy chain, DIMETHYL SULFOXIDE, ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 27837.96

Authors

Yokota, A.,Tanaka, Y.,Tsumoto, K. (deposition date: 2006-11-08, release date: 2007-11-13, Last modification date: 2023-10-25)

Primary citation

Tsumoto, K.,Yokota, A.,Tanaka, Y.,Ui, M.,Tsumuraya, T.,Fujii, I.,Kumagai, I.,Nagumo, Y.,Oguri, H.,Inoue, M.,Hirama, M.
Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49.
J.Biol.Chem., 283:12259-12266, 2008

PubMed Abstract: To address how proteins recognize polyether toxin compounds, we focused on the interaction between the ABC ring compound of ciguatoxin 3C and its specific antibody, 1C49. Surface plasmon resonance analyses indicated that Escherichia coli-expressed variable domain fragments (Fv) of 1C49 had the high affinity constants and slow dissociation constants typical of antigen-antibody interactions. Linear van't Hoff analyses suggested that the interaction is enthalpy-driven. We resolved the crystal structure of 1C49 Fv bound to ABC ring compound of ciguatoxin 3C at a resolution of 1.7A. The binding pocket of the antibody had many aromatic rings and bound the antigen by shape complementarity typical of hapten-antibody interactions. Three hydrogen bonds and many van der Waals interactions were present. We mutated several residues of the antibody to Ala, and we used surface plasmon resonance to analyze the interactions between the mutated antibodies and the antigen. This analysis identified Tyr-91 and Trp-96 in the light chain as hot spots for the interaction, and other residues made incremental contributions by conferring enthalpic advantages and reducing the dissociation rate constant. Systematic mutation of Tyr-91 indicated that CH-pi and pi-pi interactions between the aromatic ring at this site and the antigen made substantial contributions to the association, and van der Waals interactions inhibited dissociation, suggesting that aromaticity and bulkiness are critical for the specific recognition of polyether compounds by proteins.

PubMed: 18326040
DOI: 10.1074/jbc.M710553200

Experimental method

X-RAY DIFFRACTION (1.7 Å)