Structures of the antibody 64M-5 Fab and its complex with dT(6-4)T indicate induced-fit and high-affinity mechanisms.
Structures of the antibody 64M-5 Fab and its complex with dT(6-4)T indicate induced-fit and high-affinity mechanisms.
复制标题
抗体 64M-5 Fab 及其与 dT(6-4)T 的复合物的结构表明诱导拟合和高亲和力机制。
DOI：
10.1107/s2053230x18017661
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hayashida N.
中科院分区：
文献类型：
--
作者：
Yokoyama H;Mizutani R;Noguchi S;Hayashida N.
紫外线产生的带有 (6-4) 嘧啶-嘧啶酮加合物的 DNA 光产物具有致突变性和致癌性。抗 (6–4) 光产物抗体 64M-5 Fab 及其与 dT(6–4)T 复合物的晶体结构分别以 2.5 和 2.0 Å 分辨率测定。 dT(6–4)T 配体和未配体结构之间的比较表明，His93L 的侧链在与 dT(6–4)T 结合时发生极大的旋转和移动，导致与 dT(6–4)T 的磷酸部分形成静电相互作用，显示出显着的诱导拟合。根据 64M-5 和 64M-2 Fab 的 dT(6–4)T 配体结构的比较，64M-5 中的 His93L 侧链与 dT(6–4)T 的磷酸部分之间的静电相互作用在 64M-2 中的 Leu93L 中丢失，而 64M-5 中的 Arg90L 而不是 64M-5 中的 Gln90L 64M-2 稳定构象 互补决定区 (CDR) L3。与 64M-2 相比，这些差异导致 64M-5 对 dT(6–4)T 的亲和力更高。
DNA photoproducts with (6–4) pyrimidine–pyrimidone adducts produced by ultraviolet light are mutagenic and carcinogenic. The crystal structures of the anti-(6–4) photoproduct antibody 64M-5 Fab and of its complex with dT(6–4)T were determined at 2.5 and 2.0 Å resolution, respectively. A comparison between the dT(6–4)T-liganded and unliganded structures indicates that the side chain of His93L is greatly rotated and shifted on binding to dT(6–4)T, leading to the formation of an electrostatic interaction with the phosphate moiety of dT(6–4)T, which shows a remarkable induced fit. Based on a comparison of the dT(6–4)T-liganded structures of the 64M-5 and 64M-2 Fabs, the electrostatic interaction between the side chain of His93L in 64M-5 and the phosphate moiety of dT(6–4)T is lost for Leu93L in 64M-2, while Arg90L in 64M-5 instead of Gln90L in 64M-2 stabilizes the conformation of complementarity-determining region (CDR) L3. These differences contribute to the higher affinity of 64M-5 for dT(6–4)T compared with that of 64M-2.