1I7Z

ANTIBODY GNC92H2 BOUND TO LIGAND


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of a cocaine-binding antibody.

Larsen, N.A.Zhou, B.Heine, A.Wirsching, P.Janda, K.D.Wilson, I.A.

(2001) J Mol Biol 311: 9-15

  • DOI: https://doi.org/10.1006/jmbi.2001.4839
  • Primary Citation of Related Structures:  
    1I7Z

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CHIMERA OF IG KAPPA CHAIN: HUMAN CONSTANT REGION AND MOUSE VARIABLE REGION
A, C
219Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01834 (Homo sapiens)
Explore P01834 
Go to UniProtKB:  P01834
PHAROS:  P01834
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01834
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CHIMERA OF IG GAMMA-1 CHAIN: HUMAN CONSTANT REGION AND MOUSE VARIABLE REGION
B, D
220Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01857 (Homo sapiens)
Explore P01857 
Go to UniProtKB:  P01857
PHAROS:  P01857
GTEx:  ENSG00000211896 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01857
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
COC PDBBind:  1I7Z Kd: 400 (nM) from 1 assay(s)
Binding MOAD:  1I7Z Kd: 400 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.220 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 142.02α = 90
b = 64.07β = 123.06
c = 129.37γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-08-08
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description