RELATION OF STRUCTURE TO FUNCTION OF ENZYMES

我们建议继续研究酶的结构和功能 参与调节碳水化合物代谢， 激素作用和肌肉收缩。 具体来说，我们感兴趣的是 在：1）磷酸化酶磷酸酶的结构，一种可能 在糖原合成和分解的控制中发挥核心作用， 胰岛素可能参与其调节。 酶存在于 以非活性形式存在，并通过各种机制激活 正在接受调查。 2)cAMP依赖性蛋白激酶的结晶 催化亚基和确定的结构和功能 磷酸化酶激酶，特别侧重于表征 它的催化位点和其他亚基的作用。 3)结构 蛋白质的热稳定蛋白质抑制剂的生理功能 从骨骼肌中分离出来的激酶。 一个新项目 与微管冷稳定性有关的研究已经开始。 尝试 分离和表征了许多与微管相关的 参与这一过程的蛋白质，并确定它们的活性如何 通过磷酸化-去磷酸化反应进行调节， 钙调蛋白依赖性和非依赖性激酶。

We propose to continue our studies on the structure and function of enzymes involved in the regulating of carbohydrate metabolism in relation to hormone action and muscle contraction. Specifically, we are interested in: 1) The architecture of phosphorylase phosphatase, an enzyme that might play a central role in the control of glycogen synthesis and breakdown and the possible involvement of insulin in its regulation. The enzyme exists in an inactive form and the various mechanisms by which it can be activated are being investigated. 2) Crystallizing the cAMP-dependent protein kinase catalytic subunit and determining the structure and function of phosphorylase kinase with particular emphasis on the characterization of its catalytic sites and the role of its other subunits. 3) The structure and physiological function of a heat-stable protein inhibitor of protein kinase that has been isolated from skeletal muscle. A new project concerned with microtubule cold-stability has been initiated. Attempts are being made to isolate and characterize a number of microtubule-associated proteins involved in this process and to determine how their activity might be modulated by phosphorylation-dephosphorylation reactions catalyzed by calmodulin-dependent and independent kinases.