A conserved helix motif complements the protein kinase core.
Residues 40-300 of the mammalian catalytic (C) subunit of cAMP-dependent protein kinase define a conserved bilobal catalytic core shared by all eukaryotic protein kinases. Contiguous to the core is an extended amphipathic alpha-helix (A helix). Trp30, a prominent feature of this helix, fills a deep hydrophobic pocket between the two lobes on the surface opposite to the active site. The C subunit in Dictyostelium discoideum shows sequence conservation of residues 40-350 with the mouse enzyme but contains an N-terminal extension of 332 residues. A sequence corresponding to the A helix contiguous to the core is absent. However, we have now identified a remote A-helix motif (residues 77-98). When the core of the Dictyostelium C subunit was modeled, based on the mouse C subunit, complementarity between this putative A helix and the surface of the core was found to be conserved. Analysis of other protein kinases reveals that the A-helix motif is not restricted to cAMP-dependent protein kinase. In the Src-related family of protein kinases, for example, an A helix is very likely contiguous to the core, thus serving as a linker between the conserved catalytic core and the Src homology 2 domain. We predict that an A-helix motif complementary to the core will be a conserved feature of most eukaryotic protein kinases.
Veron
M
M
Unité de Biochimie Cellulaire, Centre National de la Recherche Scientifique: URA1129, Institut Pasteur, France.
Radzio-Andzelm
E
E
Tsigelny
I
I
Ten Eyck
L F
LF
Taylor
S S
SS
D000595:Amino Acid Sequence; D000818:Animals; D047388:Casein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D004023:Dictyostelium / Q000201:enzymology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D047388:Casein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases