CATALYTIC SUBUNIT OF CAMP DEPENDENT PROTEIN KINASE

蛋白激酶构成了一个庞大而多样的酶家族。 一个成员是环腺苷的催化（C）亚基 单磷酸（cAMP）依赖性蛋白激酶（cAPK）。 在没有 在cAMP的作用下，酶被隔离为无活性的四聚体复合物 含有调节亚基（R）和催化亚基。 结合后 在cAMP的作用下，全酶（R2 C2）解离成R-cAMP二聚体， 两个活跃的单体C亚基 最近，我们解决了 与腺苷复合的rC亚基的第一次， 没有肽抑制剂。 此外，我们还解决了 rC-亚基与有效的天然产物抑制剂。 这些结构 开始为基于结构的药物设计奠定基础。 的 这种APO形式结构化溶液将大大提高我们的 结构域运动，蛋白质构象变化和 也为药物设计提供了更好的起点。

Protein kinases constitute a large and diverse family of enzymes. One member is the catalytic (C) subunit of cyclic adenosine monophosphate (cAMP) dependent protein kinase (cAPK). In the absence of cAMP, the enzyme is sequestered as an inactive tetrameric complex containing both regulatory (R) and catalytic subunits. Upon binding of cAMP, the holoenzyme (R2C2) dissociates into an R-cAMP dimer and two active, monomeric C subunits. Recently, we have solved structures of the rC-subunit complexed with adenosine and for the first time without peptide inhibitor. Also, we have solved the structure of the rC-subunit with a potent natural product inhibitor. These structures are beginning to lay the basis for structure based drug design. The structure solution of this apo form would greatly enhance our knowledge on the domain movements, protein conformational changes and also give better starting points for drug design.