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Deciphering the Structural Basis of Eukaryotic Protein Kinase Regulation
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نویسنده
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meharena h.s. ,chang p. ,keshwani m.m. ,oruganty k. ,nene a.k. ,kannan n. ,taylor s.s. ,kornev a.p.
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منبع
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plos biology - 2013 - دوره : 11 - شماره : 10
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چکیده
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Eukaryotic protein kinases (epks) regulate numerous signaling processes by phosphorylating targeted substrates through the highly conserved catalytic domain. our previous computational studies proposed a model stating that a properly assembled nonlinear motif termed the regulatory (r) spine is essential for catalytic activity of epks. here we define the required intramolecular interactions and biochemical properties of the r-spine and the newly identified shell that surrounds the r-spine using site-directed mutagenesis and various in vitro phosphoryl transfer assays using cyclic amp-dependent protein kinase as a representative of the entire kinome. analysis of the 172 available apo epk structures in the protein data bank (pdb) revealed four unique structural conformations of the r-spine that correspond with catalytic inactivation of various epks. elucidating the molecular entities required for the catalytic activation of epks and the identification of these inactive conformations opens new avenues for the design of efficient therapeutic epk inhibitors. © 2013 meharena et al.
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آدرس
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biomedical sciences,university of california,san diego,la jolla,ca, United States, department of chemistry and biochemistry,university of california,san diego,la jolla,ca, United States, department of pharmacology,university of california,san diego,la jolla,ca, United States, department of biochemistry and molecular biology,university of georgia,athens,ga,united states,institute of bioinformatics,university of georgia,athens,ga, United States, department of chemistry and biochemistry,university of california,san diego,la jolla,ca, United States, department of biochemistry and molecular biology,university of georgia,athens,ga,united states,institute of bioinformatics,university of georgia,athens,ga, United States, biomedical sciences,university of california,san diego,la jolla,ca,united states,department of chemistry and biochemistry,university of california,san diego,la jolla,ca,united states,department of pharmacology,university of california,san diego,la jolla,ca,united states,howard hughes medical institute,university of california,san diego,la jolla,ca, United States, department of pharmacology,university of california,san diego,la jolla,ca,united states,howard hughes medical institute,university of california,san diego,la jolla,ca, United States
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Authors
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