Epitope mapping of ligand-receptor interactions by diffusion NMR.
Epitope mapping of ligand-receptor interactions by diffusion NMR.
复制标题
通过扩散 NMR 进行配体-受体相互作用的表位作图。
DOI：
10.1021/ja0264347
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发表时间：
2002
影响因子：
15
通讯作者：
M. Shapiro
中科院分区：
文献类型：
--
作者：
Jiangli Yan;A. Kline;H. Mo;E. Zartler;M. Shapiro
提出了一种基于扩散核磁共振的配体结合表位定位新方法。分子间NOE在长扩散期间积累，并产生线性偏差。最接近蛋白质的配体质子在扩散期间从蛋白质产生最强的NOE，并且具有最大的偏差。因此，该扩散伪影可用于表征配体结合表位。利用二氢叶酸还原酶（DHFR）及其配体甲氧苄氨嘧啶（TMP）研究了这一概念，用这种方法生成的TMP对DHFR的表位图与晶体学和NMR的结构和动力学研究以及药物化学结果非常一致。
A novel method based on diffusion NMR for the epitope mapping of ligand binding is presented. The intermolecular NOE builds up during a long diffusion period and creates a deviation from the linearity. The ligand proton nearest the protein generates the strongest NOE from protein during the diffusion period and has the largest deviation. Therefore, this diffusion artifact can be used to characterize the ligand binding epitope. The concept was investigated using dihydrofolate reductase (DHFR) and its ligand trimethoprim (TMP), and the epitope map of TMP on DHFR generated with this method is in excellent agreement with the structural and dynamic studies by crystallography and NMR, as well as the medicinal chemistry results.