1i7z
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Murine monoclonal antibody GNC92H2 was elicited by active immunization | + | 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== | ==Disease== | ||
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[[Category: Mus musculus and homo sapiens]] | [[Category: Mus musculus and homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Larsen, N | + | [[Category: Larsen, N A.]] |
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
[[Category: COC]] | [[Category: COC]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
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[[Category: igg fold]] | [[Category: igg fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:02 2008'' |
Revision as of 11:09, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 13:09:02 2008
