1i7z

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1i7z, resolution 2.3Å

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ANTIBODY GNC92H2 BOUND TO LIGAND

Contents

Overview

Murine monoclonal antibody GNC92H2 was elicited by active immunization, with a cocaine immunoconjugate and binds free cocaine with excellent, specificity and moderate affinity. Improvement of affinity, as well as, humanization of GNC92H2, would be advantageous in immunopharmacotherapy, for cocaine addiction, and for emergency cases of drug overdose. Toward, this end, the crystal structure of an engineered murine-human chimeric Fab, of GNC92H2 complexed with cocaine was determined at 2.3 A resolution., Structural analysis reveals a binding pocket with high shape and charge, complementarity to the cocaine framework, which explains the specificity, for cocaine, as opposed to the pharmacologically inactive cocaine, metabolites. Importantly, the structure provides a foundation for, mutagenesis to enhance the binding affinity for cocaine and potent cocaine, derivatives, such as cocaethylene, and for additional humanization of the, antibody.

Disease

Known disease associated with this structure: Kappa light chain deficiency OMIM:[147200]

About this Structure

1I7Z is a Protein complex structure of sequences from Mus musculus and homo sapiens with COC as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of a cocaine-binding antibody., Larsen NA, Zhou B, Heine A, Wirsching P, Janda KD, Wilson IA, J Mol Biol. 2001 Aug 3;311(1):9-15. PMID:11469854

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