MOLECULAR INTERACTIONS OF CALMODULIN WITH TARGET ENZYMES

钙调蛋白是一种已知的细胞内钙结合蛋白 为了调节体内许多不同的酶的活性 以钙依赖的方式。其中许多依赖于钙调蛋白的酶 已知在细胞的功能中具有重要的生物化学作用 心肺系统的各种组织。然而，几乎没有什么是 目前已知的分子水平上的相互作用 钙调蛋白及其靶标酶。该基因的氨基酸序列 一种钙调素依赖蛋白的钙调蛋白结合区 肌球蛋白轻链激酶(MLCK)酶最近被 与该序列相对应的确定的和合成的多肽 已经做好了准备。这些MLCK钙调蛋白结合肽出现 与钙调蛋白的相互作用方式与天然钙调素基本相同 蛋白质，因此是研究钙调蛋白的有用模型 靶向酶在分子水平上的相互作用。目的 本研究的目的是开发合成MLCK文库 包含一系列不同分子探针的多肽 多肽序列中的特定位置。这个图书馆的 标记的多肽将被用来表征多肽-钙调蛋白 更详细的互动。这些研究可以扩展到 其他依赖钙调蛋白的酶，并应为 了解钙调蛋白调节过程的机制。 可以想象，从这些研究中获得的信息 将有助于开发可用于治疗的药剂 在治疗高血压和哮喘等疾病时 已知涉及钙调蛋白调节的过程。

Calmodulin is an intracellular Ca++binding protein that is known to regulate the activities of a number of different enzymes in a Ca++-dependent manner. Many of these calmodulin-dependent enzymes are known to have significant biochemical roles in the function of various tissues of the cardiopulmonary system. However, little is presently known at the molecular level about the interactions of calmodulin with its target enzymes. The amino acid sequence of the calmodulin-binding domain of one well-studied calmodulin-dependent enzyme, myosin light chain kinase (MLCK), has recently been determined and synthetic peptides corresponding to this sequence have been prepared. These MLCK calmodulin-binding peptides appear to interact with calmodulin in much the same way as the native protein and are therefore useful models for studying calmodulin-- target enzyme interactions at the molecular level. The purpose of the proposed research is to develop a library of synthetic MLCK peptides containing an assortment of different molecular probes at specific positions within the peptide sequence. This library of labeled peptides will be used to characterize peptide-calmodulin interactions in some detail. These studies can be extended to other calmodulin-dependent enzymes and should provide a basis for understanding the mechanisms of calmodulin-regulated processes. It is conceivable that the information gained from these studies will be useful in developing therapeutic agents that could be used in the treatment of diseases such as hypertension and asthma where calmodulin-regulated processes are known to be involved.