title: A helix scaffold for the assembly of active protein kinases.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Alexandr P
authors.initials: AP
authors.lastname: Kornev
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Ten Eyck
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D019295:Computational Biology; D008958:Models, Molecular; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D011494:Protein Kinases
references.citation: FEBS Lett. 1999 Sep 10;458(1):69-71
references.pmid: 10518936
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18101-6
references.pmid: 17114285
references.citation: Hum Mutat. 2005 May;25(5):435-42
references.pmid: 15832311
references.citation: Chem Rev. 2001 Aug;101(8):2243-70
references.pmid: 11749372
references.citation: Bioinformatics. 2004 Apr 12;20(6):863-73
references.pmid: 14752003
references.citation: J Biol Chem. 2003 Mar 21;278(12):10613-8
references.pmid: 12499371
references.citation: J Mol Biol. 2005 Feb 11;346(1):191-201
references.pmid: 15663937
references.citation: EMBO J. 2008 Feb 20;27(4):704-14
references.pmid: 18239682
references.citation: J Biol Chem. 2005 Apr 8;280(14):13993-4005
references.pmid: 15695825
references.citation: Cell. 2007 Sep 21;130(6):1032-43
references.pmid: 17889648
references.citation: Trends Biochem Sci. 2002 Oct;27(10):514-20
references.pmid: 12368087
references.citation: PLoS Comput Biol. 2005 Oct;1(5):e49
references.pmid: 16244704
references.citation: J Mol Biol. 2005 Oct 28;353(3):600-12
references.pmid: 16185715
references.citation: J Biol Chem. 2005 Mar 11;280(10):8800-7
references.pmid: 15618230
references.citation: FASEB J. 1995 May;9(8):576-96
references.pmid: 7768349
references.citation: Science. 2007 Oct 12;318(5848):274-9
references.pmid: 17932298
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9
references.pmid: 1438297
references.citation: Biochemistry. 2000 May 9;39(18):5366-73
references.pmid: 10820007
references.citation: Mol Cell. 2001 Mar;7(3):615-26
references.pmid: 11463386
references.citation: J Phys Chem B. 2007 Nov 29;111(47):13455-64
references.pmid: 17983217
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17783-8
references.pmid: 17095602
references.citation: PLoS Comput Biol. 2008 Apr 11;4(4):e1000056
references.pmid: 18404204
references.citation: J Biol Chem. 2005 Oct 28;280(43):36372-9
references.pmid: 16131491
references.citation: Biochemistry. 2007 May 15;46(19):5687-96
references.pmid: 17441692
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):45-50
references.pmid: 15618393
references.citation: J Mol Biol. 2005 Sep 2;351(5):956-72
references.pmid: 16051269
references.citation: Curr Opin Struct Biol. 2006 Feb;16(1):102-8
references.pmid: 16423525
references.citation: Protein Sci. 2005 Nov;14(11):2871-9
references.pmid: 16253959
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):506-11
references.pmid: 18178622
references.citation: Biochemistry. 2001 Jul 31;40(30):8756-64
references.pmid: 11467935
references.citation: Bioessays. 1999 Nov;21(11):932-9
references.pmid: 10517866
references.citation: Nat Struct Biol. 2003 Jan;10(1):59-69
references.pmid: 12483203
references.citation: Cell. 2002 May 3;109(3):275-82
references.pmid: 12015977