TRANSPORT OF SULFONYL UREA DERIVATIVES BY TIME RESOLVED FLUORESCENCE METHODS

我们正在研究结构，平衡动力学，以及 人催乳素的折叠。催乳素是由199个残基组成的 血液性细胞因子家族，包括生长激素。 催乳素与许多生化途径有关，但 它的名字是因为它在怀孕期间促进哺乳的作用。 生长激素和生长激素结合的X射线结构 催乳素受体的胞外结构域给出了一些见解 造血激素作用的一般特征；原住民 结构是一个四股螺旋束，具有不寻常的向上-向上-向下-向下 拓扑学，它通过诱导感受器的二聚化起作用 两步顺序装订过程。生长激素与两种细胞结合 躯体受体和催乳素受体。相比之下， 催乳素只与催乳素受体结合。此外，锌是 已知可调节生长激素的受体结合，而它确实如此 似乎不在催乳素结合中起作用。催乳素因此 到目前为止，还没有详细的结构分析，所以分子细节 生长激素和生长激素行为的不同 催乳素仍未得到解释。我们正在践行这一决心 高分辨多核技术研究催乳素的溶液结构 核磁共振。我们正在研究催乳素的折叠和稳定性 利用平衡离心法、圆二色谱、扫描 量热法和氢交换动力学。ESI和NLkLDI质量 光谱分析用于测定蛋白质的相对分子质量和 二硫键连接的位置。

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.