PDBsum entry 3g6d

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Immune system PDB id
Jmol PyMol
Protein chains
210 a.a. *
223 a.a. *
106 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of the complex between cnto607 fab and il-
Structure: Cnto607 fab light chain. Chain: l. Engineered: yes. Cnto607 fab heavy chain. Chain: h. Engineered: yes. Interleukin-13. Chain: a. Fragment: unp residues 21-132.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293. Expression_system_organ: kidney. Expression_system_cell: human embryonic kidney 293 cells. Gene: il13, nc30.
3.20Å     R-factor:   0.213     R-free:   0.263
Authors: A.Teplyakov,G.Obmolova,G.L.Gilliland
Key ref:
A.Teplyakov et al. (2009). Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607. J Mol Biol, 389, 115-123. PubMed id: 19361524 DOI: 10.1016/j.jmb.2009.03.076
06-Feb-09     Release date:   07-Apr-09    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 210 a.a.
Protein chain
No UniProt id for this chain
Struc: 223 a.a.
Protein chain
Pfam   ArchSchema ?
P35225  (IL13_HUMAN) -  Interleukin-13
146 a.a.
106 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     cellular response to mechanical stimulus   31 terms 
  Biochemical function     protein binding     4 terms  


DOI no: 10.1016/j.jmb.2009.03.076 J Mol Biol 389:115-123 (2009)
PubMed id: 19361524  
Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607.
A.Teplyakov, G.Obmolova, S.J.Wu, J.Luo, J.Kang, K.O'Neil, G.L.Gilliland.
CNTO607 is a neutralizing anti-interleukin-13 (IL-13) human monoclonal antibody obtained from a phage display library. To determine how this antibody inhibits the biological effect of IL-13, we determined the binding epitope by X-ray crystallography. The crystal structure of the complex between CNTO607 Fab and IL-13 reveals the antibody epitope at the surface formed by helices A and D of IL-13. This epitope overlaps with the IL-4Ralpha/IL-13Ralpha1 receptor-binding site, which explains the neutralizing effect of CNTO607. The extensive antibody interface covers an area of 1000 A(2), which is consistent with the high binding affinity. The key features of the interface are the charge and shape complementarity of the molecules that include two hydrophobic pockets on IL-13 that accommodate Phe32 [complementarity-determining region (CDR) L2] and Trp100a (CDR H3) and a number of salt bridges between basic residues of IL-13 and acidic residues of the antibody. Comparison with the structure of the free Fab shows that the CDR residues do not change their conformation upon complex formation, with the exception of two residues in CDR H3, Trp100a and Asp100b, which change rotamer conformations. To evaluate the relative contribution of the epitope residues to CNTO607 binding, we performed alanine-scanning mutagenesis of the A-D region of IL-13. This study confirmed the primary role of electrostatic interactions for antigen recognition.
  Selected figure(s)  
Figure 2.
Fig. 2. Electron density in the IL-13/Fab interface around CDR L1.
Figure 4.
Fig. 4. IL-13 interaction with the receptor and CNTO607. (a) IL-13 complex with IL-4Rα/IL-13Rα1 receptor.^19 (b) IL-13 complex with CNTO607 Fab. IL-13 is in the same orientation as in (a). Structural domains and helices in IL-13 are labeled.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 389, 115-123) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20543007 S.J.Wu, J.Luo, K.T.O'Neil, J.Kang, E.R.Lacy, G.Canziani, A.Baker, M.Huang, Q.M.Tang, T.S.Raju, S.A.Jacobs, A.Teplyakov, G.L.Gilliland, and Y.Feng (2010).
Structure-based engineering of a monoclonal antibody for improved solubility.
  Protein Eng Des Sel, 23, 643-651.  
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