TRANSPORT OF SULFONYL UREA DERIVATIVES BY TIME RESOLVED FLUORESCENCE METHODS

通过时间分辨荧光方法传输磺酰脲衍生物

• 批准号: 6345218
• 负责人: JAMES Athur HAMILTON
• 金额: $ 0.49万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6345218
• 关键词: biological products; biomedical resource; clinical research; female; hormones; human subject; mother /infant health care; reproductive system; spectrometry; structural biology; women's health

We are investigating the structure, equilibrium dynamics, and folding of human prolactin. Prolactin is a 199-residue member of the hernatopoietic cytokine family, which includes growth hormone. Prolactin is implicated in a large number of biochemical pathways, but it is named for its role in promoting lactation during pregnancy. X-ray structures of growth hormone andgrowth hormone bound to the extracellular domain of the lactogenic receptor have given insights into the general features of hematopoietic hormone action; the native structure is a four-helix bundle with an unusual up-up-down-down topology, and it acts by inducing dimerization of thereceptor in a two-step sequential binding process. Growth hormone binds to both the somatogenic receptor and to the lactogenic receptor. In contrast, prolactin binds only to the lactogenic receptor. In addition, zinc is known to mediate receptor binding of growth hormone, whereas it does not appear to play a role in prolactin binding. Prolactin has thus far eluded detailed structural analysis, and so the molecular details responsible for the difference in the behavior of growth hormone and prolactin remain unexplained. We are carrying out the determination of the solution structure of prolactin by high resolution multinuclear NMR. We are investigating the folding and stability of prolactin using equilibrium centrifugation, circular dichroism, scanning calorimetry, and hydrogen exchange kinetics. ESI and NLkLDI mass spectrometry are used to determine the protein molecular weight and sites of disulfide linkage.

我们正在研究结构、平衡动力学和 人类催乳素的折叠。 催乳素是具有 199 个残基的成员 造血细胞因子家族，其中包括生长激素。 催乳素与大量生化途径有关，但是 它因其在怀孕期间促进泌乳的作用而得名。 生长激素和生长激素结合的 X 射线结构 催乳受体的细胞外结构域给出了见解 造血激素作用的一般特征；本地人 结构是一个四螺旋束，具有不寻常的上上下下 拓扑结构，它通过诱导受体二聚化来起作用 两步顺序绑定过程。 生长激素与两者结合 促生长受体和促泌乳受体。 相比之下， 催乳素仅与催乳受体结合。 此外，锌是 已知介导生长激素受体结合，而它确实 似乎在催乳素结合中不起作用。 催乳素因此 远远无法进行详细的结构分析，因此分子细节 造成生长激素行为差异的原因 催乳素仍然无法解释。 我们正在执行决心 高分辨率多核催乳素溶液结构 核磁共振。 我们正在研究催乳素的折叠和稳定性 使用平衡离心、圆二色性、扫描 量热法和氢交换动力学。 ESI 和 NLkLDI 质量 光谱法用于测定蛋白质的分子量和 二硫键位点。