Rose D R, Strong R K, Margolies M N, Gefter M L, Petsko G A
Division of Biological Sciences, National Research Council of Canada, Ottawa, ON.
Proc Natl Acad Sci U S A. 1990 Jan;87(1):338-42. doi: 10.1073/pnas.87.1.338.
The structure of the antigen-binding fragment (Fab) of an anti-phenylarsonate monoclonal antibody (36-71) bearing a major crossreacting idiotype of A/J mice has been solved and refined to an R factor of 19.3% at a resolution of 2.9 A. An initial electron density map was obtained with phase information from a total of six isomorphous heavy-atom derivatives (from two different compounds) and a molecular replacement solution using the HED10 Fab crystal structure as a model. The structure of the McPC603 Fab was used to provide an initial set of atomic coordinates. The electron density maps are clear and easily interpretable for the entire sequence except for sections from two of the heavy-chain complementarity-determining regions totaling 21 residues. These residues have been left out of the refinement and are not represented in our current model. The antigen-combining site was located by means of a difference Fourier synthesis with one of the heavy-atom derivatives, which contained arsanilic acid. It lies in a small pocket formed by residues from the hypervariable regions of both the heavy and the light chains. Interactions with the hapten from framework residues are also possible.
已解析并精修了携带A/J小鼠主要交叉反应独特型的抗苯胂酸单克隆抗体（36 - 71）的抗原结合片段（Fab）结构，在2.9埃分辨率下R因子为19.3%。利用来自总共六种同晶型重原子衍生物（来自两种不同化合物）的相位信息以及以HED10 Fab晶体结构为模型的分子置换解决方案，获得了初始电子密度图。使用McPC603 Fab的结构提供了一组初始原子坐标。除了两条重链互补决定区共21个残基的片段外，整个序列的电子密度图清晰且易于解读。这些残基未纳入精修，在我们当前的模型中也未体现。通过与含有对氨基苯胂酸的一种重原子衍生物进行差值傅里叶合成确定了抗原结合位点。它位于由重链和轻链高变区的残基形成的一个小口袋中。骨架残基与半抗原之间也可能存在相互作用。
