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)亚单位 一磷酸(CAMP)依赖的蛋白激酶(CAPK)。在缺席时 在cAMP中，酶以不活跃的四聚体络合物的形式被隔离。 含有调节性(R)和催化亚基。在绑定时 CAMP的全酶(R2C2)解离成R-cAMP二聚体， 两个活跃的单体C亚基。最近，我们已经解决了结构 Rc亚基与腺苷的络合，并首次 不含多肽抑制剂。此外，我们还解决了 RC-亚基与一种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。这个 这种载脂蛋白的结构解决方案将极大地增强我们的 了解结构域移动、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.