The structural basis for the function of two anti-VEGF receptor 2 antibodies.
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Franklin MC, Navarro EC, 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. 2011 Aug 10;19(8):1097-107. doi: 10.1016/j.str.2011.01.019.
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- 21827946 [ View in 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.