Gamboni S, Chaperon C, Friedrich K, Baehler P J, Reymond C D
Institut de biologie cellulaire et de morphologie, Lausanne, Switzerland.
Biochemistry. 1998 Sep 1;37(35):12189-94. doi: 10.1021/bi980028b.
The catalytic subunit of the cAMP-dependent protein kinase from Dictyostelium discoideum, PkaC, displays the same properties as its mammalian counterpart, except for being about twice as large in size. Sequence comparisons indicated the presence of a conserved alpha-helix (A-helix) within the N-terminal region of PkaC which could potentially establish close contacts with the catalytic core [Véron, M., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10618-10622]. We show in this report that a synthetic peptide with the A-helix sequence inhibits PKA activity, whereas unrelated peptides display no inhibitory activity. The inhibition seems competitive with respect to the kemptide substrate rather than due to binding to a secondary site. We further show by amino acid replacements that the last lysine of the A-helix sequence is involved in this specific inhibition. A model is proposed for the possible role of the A-helix.
盘基网柄菌中依赖环磷酸腺苷（cAMP）的蛋白激酶的催化亚基PkaC，除了大小约为其哺乳动物对应物的两倍外，表现出与其相同的特性。序列比较表明，PkaC的N端区域存在一个保守的α螺旋（A螺旋），它可能与催化核心建立紧密接触[Véron, M.,等人（1993年）《美国国家科学院院刊》90, 10618 - 10622]。我们在本报告中表明，具有A螺旋序列的合成肽抑制PKA活性，而不相关的肽则没有抑制活性。这种抑制似乎相对于kemptide底物是竞争性的，而不是由于与二级位点结合。我们通过氨基酸替换进一步表明，A螺旋序列的最后一个赖氨酸参与了这种特异性抑制。提出了一个关于A螺旋可能作用的模型。
