The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies
The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies
复制标题
DOI：
10.1016/j.str.2011.01.019
复制
发表时间：
2011-08-10
期刊：
影响因子：
5.7
通讯作者：
Kussie, Paul
中科院分区：
文献类型：
--
作者：
Franklin, Matthew C.;Navarro, Elizabeth C.;Kussie, Paul
抗VEGF受体2抗体IMC-1121 B是一种有前途的抗血管生成药物，正在测试用于治疗乳腺癌和胃癌。我们已经确定了与VEGFR 2结构域3复合的1121 B Fab片段的结构，以及也与VEGFR 2结构域3复合的不同中和性抗VEGFR 2抗体6.64的结构。两个Fab片段在VEGFR 2结构域3的相对末端结合; 1121 B直接阻断VEGF结合，而6.64可以通过干扰结构域3：结构域4界面来防止受体二聚化。突变显示，VEGF，1121 B和6.64结合所必需的残基在三个接触斑之间是不重叠的。
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 nonover-lapping among the three contact patches.