3s37

Publication Abstract from PubMed

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.

The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies.,Franklin MC, Navarro EC, Wang Y, Patel S, Singh P, Zhang Y, Persaud K, Bari A, Griffith H, Shen L, Balderes P, Kussie P Structure. 2011 Aug 10;19(8):1097-107. PMID:21827946^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.