University of Maryland, Department of Pharmaceutical Sciences, Baltimore, MD 21201, United States.
Bioorg Med Chem. 2010 Sep 15;18(18):6756-62. doi: 10.1016/j.bmc.2010.07.051. Epub 2010 Jul 27.
Histidine triad nucleotide binding protein (HINT1) is an intracellular protein that binds purine mononucleotides. Strong sequence conservation suggests that these proteins play a fundamental role in cell biology, however its exact cellular function continues to remain elusive. nuclear magnetic resonance (NMR) studies using STD and HSQC were conducted to observe ligand binding to HINT1. These studies were confirmed using fluorescence spectroscopy titrations. We found that AICAR, the first non-phosphate containing ligand, binds to mouse histidine triad nucleotide binding protein 1 (HINT1). Chemical shift perturbations are mapped onto the X-ray structure showing AICAR binds at the same site as GMP. The NMR results demonstrated that this method will be valuable for the future screening of small molecules that can be used to modulate the function of HINT1.
组氨酸三联核苷酸结合蛋白（HINT1）是一种能结合嘌呤单核苷酸的细胞内蛋白。强烈的序列保守性表明这些蛋白在细胞生物学中发挥着基本作用，但它的确切细胞功能仍难以捉摸。使用 STD 和 HSQC 的核磁共振（NMR）研究来观察配体与 HINT1 的结合。这些研究使用荧光光谱滴定法得到了证实。我们发现，第一个非磷酸类配体 AICAR 与小鼠组氨酸三联核苷酸结合蛋白 1（HINT1）结合。化学位移扰动映射到 X 射线结构上，表明 AICAR 与 GMP 结合在相同的位点。NMR 结果表明，该方法将对未来筛选可用于调节 HINT1 功能的小分子化合物具有重要价值。
