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Conserved hydrophobic ensembles in protein kinases: their integrating and regulatory roles
Author(s) -
Kornev Alexandr P.,
Ten Eyck Lynn F.,
Taylor Susan S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1048.12
Subject(s) - kinase , conserved sequence , computational biology , protein superfamily , serine , biology , protein kinase a , threonine , protein structure , biochemistry , c raf , peptide sequence , phosphorylation , cyclin dependent kinase 2 , gene
Protein kinases represent a large protein superfamily which regulates numerous processes in living cells. Structures of several serine‐threonine and tyrosine kinases were investigated by recently developed bioinformatics method: Local Spatial Patterns alignment. Previously this method proved to be an effective tool, which is capable to detect highly conserved spatial patterns of amino acid residues. These residues do not form traditional motifs in terms of sequence or protein fold and can not be detected by traditional methods. An example of that was discovery of “the spine” in protein kinases, an important regulatory element. In this work we report detailed analysis of the protein kinase catalytic core. A set of conserved ensembles comprised mostly by hydrophobic residues was detected. The formations traverse protein kinase molecules and play integrating and regulatory roles. They are anchored to the F‐helix located in the middle of the large lobe, which acts as an organizing “hub” providing exact positioning of the key catalytic and regulatory elements. This work was supported by National Science Foundation Grant NSF‐DBI 99111196 and National Institute of General Medical Sciences Grants GM70996 (to L.F.T.E.); GM19301 and National Science Foundation Grant DBI0217951 (to S.S.T.).