MOLECULAR INTERACTIONS OF CALMODULIN WITH TARGET ENZYMES

钙调素是一种细胞内Ca++结合蛋白， 调节多种不同酶的活性， Ca++依赖方式。 许多钙调素依赖酶 已知在以下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， 目前已知的分子水平上的相互作用， 钙调素及其靶酶。 的氨基酸序列 钙调素结合域的一个充分研究的钙调素依赖 肌球蛋白轻链激酶（MLCK）最近被 对应于该序列的确定的和合成的肽 已经准备好了。 这些MLCK钙调蛋白结合肽似乎 与钙调素的相互作用方式与天然的 因此是研究钙调素的有用模型-- 在分子水平上靶向酶的相互作用。 的目的 建议的研究是开发一个合成MLCK库 含有各种不同分子探针的肽， 肽序列内的特定位置。 这个图书馆 标记的肽将用于表征肽-钙调蛋白 互动的细节。 这些研究可以扩展到 其他钙调素依赖酶，并应提供基础， 了解钙调素调节过程的机制。 可以想象，从这些研究中获得的信息 将有助于开发可用于 在治疗高血压和哮喘等疾病时， 已知涉及钙调蛋白调节过程。

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.