1i7z
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7z OCA], [http://www.ebi.ac.uk/pdbsum/1i7z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1i7z RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147200 147200]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 27: | Line 27: | ||
[[Category: Larsen, N A.]] | [[Category: Larsen, N A.]] | ||
[[Category: Wilson, I A.]] | [[Category: Wilson, I A.]] | ||
| - | [[Category: COC]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
[[Category: chimera]] | [[Category: chimera]] | ||
[[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 Sun Mar 30 21:16:08 2008'' |
Revision as of 18:16, 30 March 2008
| |||||||
| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ANTIBODY GNC92H2 BOUND TO LIGAND
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.
About this Structure
1I7Z is a Protein complex structure of sequences from Mus musculus and homo sapiens. 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 Sun Mar 30 21:16:08 2008
