Ma Jichun, Tang Wai Kwan, Esser Lothar, Pastan Ira, Xia Di
Laboratory of Cell Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug 1;68(Pt 8):950-3. doi: 10.1107/S1744309112028229. Epub 2012 Jul 31.
The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 7-64) were crystallized. The crystals of the Fab diffracted X-rays to 1.75 Å resolution and had the symmetry of space group P4(1)2(1)2, with unit-cell parameters a = b = 140.6, c = 282.0 Å. The crystals of the mesothelin-Fab complex diffracted to 2.6 Å resolution and belonged to the hexagonal space group P6(4), with unit-cell parameters a = b = 146.2, c = 80.9 Å. Structural analyses of these molecules are in progress.
间皮素特异性单克隆抗体MORAb-009能够阻断间皮素与CA-125的结合，并显示出有前景的抗癌潜力。它目前正在进行临床试验。为了在原子分辨率下理解MORAb-009与间皮素之间相互作用的基础，MORAb-009的Fab片段以及Fab与间皮素N端片段（残基7 - 64）之间的复合物均被结晶。Fab的晶体将X射线衍射至1.75 Å分辨率，具有空间群P4(1)2(1)2的对称性，晶胞参数a = b = 140.6，c = 282.0 Å。间皮素 - Fab复合物的晶体衍射至2.6 Å分辨率，属于六方空间群P6(4)，晶胞参数a = b = 146.2，c = 80.9 Å。这些分子的结构分析正在进行中。
