Proceedings of the National Academy of Sciences · 2008 · 447 citations · 29 references
Life SciencesBiochemistryBioinformaticsStructural BiochemistryStructural BioinformaticsStructural BiologyMacromolecular AssemblyMotif DiscoveryProtein MotifsProtein StructureScaffold ProteinsStructural MotifsConserved Structural MotifsKinase Scaffold ProteinsProtein Motif DiscoveryProtein Motif ScaffoldingProtein ScaffoldingScaffold Proteins In Kinase CascadesSequence-structure AlignmentStructural Motif Alignment
Structures of set of serine-threonine and tyrosine kinases were investigated by the recently developed bioinformatics tool Local Spatial Patterns (LSP) alignment. We report a set of conserved motifs comprised mostly of hydrophobic residues. These residues are scattered throughout the protein sequence and thus were not previously detected by traditional methods. These motifs traverse the conserved protein kinase core and play integrating and regulatory roles. They are anchored to the F-helix, which acts as an organizing "hub" providing precise positioning of the key catalytic and regulatory elements. Consideration of these discovered structures helps to explain previously inexplicable results.
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