2AK1

Crystal Structure of Cocaine catalytic Antibody 7A1 Fab' in Complex with benzoic acid

Summary for 2AK1

• Entry DOI: 10.2210/pdb2ak1/pdb
• Related: 2AJS 2AJU 2AJV 2AJX 2AJY 2AJZ
• Descriptor: Antibody 7A1 Fab', ZINC ION, BENZOIC ACID, ... (5 entities in total)
• Functional Keywords: catalytic antibody, fab, benzoic acid, hydrolytic, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 48309.15

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2005-08-02, release date: 2006-02-14, Last modification date: 2024-10-16)

Primary citation

Zhu, X.,Dickerson, T.J.,Rogers, C.J.,Kaufmann, G.F.,Mee, J.M.,McKenzie, K.M.,Janda, K.D.,Wilson, I.A.
Complete reaction cycle of a cocaine catalytic antibody at atomic resolution.
Structure, 14:205-216, 2006

PubMed Abstract: Antibody 7A1 hydrolyzes cocaine to produce nonpsychoactive metabolites ecgonine methyl ester and benzoic acid. Crystal structures of 7A1 Fab' and six complexes with substrate cocaine, the transition state analog, products ecgonine methyl ester and benzoic acid together and individually, as well as heptaethylene glycol have been analyzed at 1.5-2.3 angstroms resolution. Here, we present snapshots of the complete cycle of the cocaine hydrolytic reaction at atomic resolution. Significant structural rearrangements occur along the reaction pathway, but they are generally limited to the binding site, including the ligands themselves. Several interacting side chains either change their rotamers or alter their mobility to accommodate the different reaction steps. CDR loop movements (up to 2.3 angstroms) and substantial side chain rearrangements (up to 9 angstroms) alter the shape and size (approximately 320-500 angstroms3) of the antibody active site from "open" to "closed" to "open" for the substrate, transition state, and product states, respectively.

PubMed: 16472740
DOI: 10.1016/j.str.2005.10.014

Experimental method

X-RAY DIFFRACTION (1.85 Å)