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Decoding the Interactions Regulating the Active State Mechanics of Eukaryotic Protein Kinases
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نویسنده
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meharena h.s. ,fan x. ,ahuja l.g. ,keshwani m.m. ,mcclendon c.l. ,chen a.m. ,adams j.a. ,taylor s.s.
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منبع
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plos biology - 2016 - دوره : 14 - شماره : 11
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چکیده
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Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. in the active state,the catalytic core oscillates between open,intermediate,and closed conformations. currently,the intramolecular interactions that regulate the active state mechanics are not well understood. here,using camp-dependent protein kinase as a representative model coupled with biochemical,biophysical,and computational techniques,we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. these include the previously identified salt bridge between a lysine from the β3-strand and a glutamate from the αc-helix as well as an electrostatic interaction between the phosphorylated activation loop and αc-helix and an ensemble of hydrophobic residues of the regulatory spine and shell. moreover,for over three decades it was thought that the highly conserved β3-lysine was essential for phosphoryl transfer,but our findings show that the β3-lysine is not required for phosphoryl transfer but is essential for the active state mechanics. © 2016 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 pharmacology,university of california,san diego,la jolla,ca, United States, department of pharmacology,university of california,san diego,la jolla,ca,united states,skaggs school of pharmacy and pharmaceutical sciences,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 pharmacology,university of california,san diego,la jolla,ca, 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
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Authors
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