Véron M, Radzio-Andzelm E, Tsigelny I, Taylor S
Unité de Biochimie Celllaire, Institut Pasteur, Paris, France.
Cell Mol Biol (Noisy-le-grand). 1994 Jul;40(5):587-96.
A comparison of the sequences of the mammalian and Dictyostelium catalytic subunits of cAMP-dependent protein kinase revealed extensive sequence similarities through the catalytic core and the carboxy terminal tail. The amino terminal sequences however differ dramatically. The large difference in size, 73 kDa for the Dictyostelium enzyme versus 40 kDa is due to an extension in the N-terminus. The mouse enzyme has at its amino-terminus a long amphipatic helix, the A-helix, that precedes the catalytic core, covering the surface of both lobes of the enzyme. Dictyostelium does in fact, have a similar motif but it is remote from the catalytic core, in the N-terminal extension. On the basis of molecular modeling, it is proposed that residues 77-98 correspond to a structural motif similar to the A-helix in mouse catalytic subunit. Sequences encoding similar putative motifs contiguous to the catalytic core can be recognized in many other protein kinases and is particularly prominent in all of the non-receptor tyrosine kinases. In the case of Src, this A-helix motif appears to serve as the linker between the conserved catalytic core and the SH2 domain. The interaction between the A-helix motif and the core is described, and the general occurrence of this structure within the protein kinase family is discussed.
对哺乳动物和盘基网柄菌环磷酸腺苷依赖性蛋白激酶催化亚基的序列进行比较后发现，在催化核心和羧基末端尾部存在广泛的序列相似性。然而，氨基末端序列却有显著差异。大小差异很大，盘基网柄菌的酶为73 kDa，而小鼠的为40 kDa，这是由于N端的延伸。小鼠酶在其氨基末端有一个长的两亲性螺旋，即A螺旋，它位于催化核心之前，覆盖酶的两个叶的表面。实际上，盘基网柄菌有一个类似的基序，但它在N端延伸部分，远离催化核心。基于分子建模，有人提出77 - 98位残基对应于一个与小鼠催化亚基中的A螺旋相似的结构基序。在许多其他蛋白激酶中可以识别出与催化核心相邻的编码类似推定基序的序列，并且在所有非受体酪氨酸激酶中尤为突出。就Src而言，这个A螺旋基序似乎充当保守催化核心与SH2结构域之间的连接物。描述了A螺旋基序与核心之间的相互作用，并讨论了这种结构在蛋白激酶家族中的普遍存在情况。
