3S36

Structural basis for the function of two anti-VEGF receptor antibodies

Summary for 3S36

• Entry DOI: 10.2210/pdb3s36/pdb
• Related: 3S34 3S37
• Descriptor: 1121B light chain, 1121B heavy chain, Vascular endothelial growth factor receptor 2 (3 entities in total)
• Functional Keywords: antibody, kdr, vegf receptor, cancer, immune system-transferase complex, immune system/transferase
• Biological source: Mus musculus, Homo sapiens (mouse, human); More
• Cellular location: Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968
• Total number of polymer chains: 3
• Total formula weight: 60074.27

Authors

Franklin, M.C. (deposition date: 2011-05-17, release date: 2011-08-24, Last modification date: 2024-10-30)

Primary citation

Franklin, M.C.,Navarro, E.C.,Wang, Y.,Patel, S.,Singh, P.,Zhang, Y.,Persaud, K.,Bari, A.,Griffith, H.,Shen, L.,Balderes, P.,Kussie, P.
The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies.
Structure, 19:1097-1107, 2011

PubMed Abstract: The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

PubMed: 21827946
DOI: 10.1016/j.str.2011.01.019

Experimental method

X-RAY DIFFRACTION (3.2 Å)