METABOLIC REGULATION AND INTERACTING ENZYME SYSTEMS

拟议研究的长期目标与以下方面有关 了解蛋白质-蛋白质相互作用在生物合成中的作用 对某些代谢过程的调节和理解 酶的结构-功能关系。具体项目和 1)肌动蛋白的聚合及肌动蛋白结合作用 聚合过程中的蛋白质以及结构中的蛋白质 和肌动蛋白凝胶在体外和体内系统中的性质；2) 红细胞微管蛋白的特性；3)红细胞膜微管蛋白的作用机制 腺苷脱氨酶和二氢叶酸还原酶的作用； 野生型蛋白质折叠的动力学和机制 二氢叶酸还原酶的定点突变体。 肌动蛋白、肌动蛋白结合蛋白和微管蛋白是直接作用的 与非肌肉细胞中的各种细胞功能相关，包括 细胞运动、细胞骨架结构、内吞作用、细胞分裂和 就这样吧。特别令人感兴趣的是建议的经验 测量已知剪应力对细胞的影响 使用数字成像技术的动力学。 腺苷脱氨酶和二氢叶酸还原酶都是靶标 用于抑制治疗药物。腺苷抑制剂 脱氨酶已用于T细胞急性白血病患者 淋巴细胞白血病与二氢叶酸抑制剂 还原酶既被用作抗菌剂，也被用作 抗癌药物可能是因为四氢叶酸 最终与DNA合成有关。折叠 建议用野生型和定点突变体进行实验 二氢叶酸还原酶可能有助于更好地理解 蛋白质中的结构-功能关系以及随后的 创造具有特定功能的新酶的能力。

The long term objectives of the proposed research are related to understanding the role of protein-protein interactions in the regulation of certain metabolic processes and to understanding structure-function relationships in enzymes. Specific projects and 1) the polymerization of actin and the role of actin binding proteins in the polymerization process as well as in the structure and nature of actin gels in both in vitro and in vivo systems; 2) the characterization of tubulin from erytrocytes; 3) the mechanism of action of adenosine deaminase and dihydrofolate reductase; and 4) the kinetics and mechanism of protein folding using wild type and site directed mutants of dihydrofolate reductase. Work with actin, actin binding proteins and tubulin is directly related to various cellular functions in non-muscle cells including cell motility, cytoskeletal structure, endocytosis, cell division and so on. Of particular interest are proposed experiemnts to measure the consequences of known shear stresses on cellular dynamics using digital imaging techniques. Both adenosine deaminase and dihydrofolate reductase are targets for inhibitory therapeutic drugs. Inhibitors of adenosine deaminase have been used in patients with T-cell acute lymphoblastic leukemia while inhibitors of dihydrofolate reductase have been used both as antibacterial agents and anticancer agents presumably because the tetrahydrofolate produced is ultimately related to DNA synthesis. The folding experiments proposed with wild type and site directed mutants of dihydrofolate reductase may lead to a better undrstanding of structure-function relationships in proteins and subsequently to the ability to create new enzymes with specific functions.