B and T Fig. 13.7Green - GTP bound (on)Blue - GDP bound (off)Active and inactive Galpha subunitsFig. 13-2 B and TAn activated G-protein then activates adenylyl cyclaseFig. 13-3 B and THormones, such as epinephrine, also activate adenylyl cyclase.Fig. 12-12LehnFig. 12-15 LehnFig. 12-16LehnProtein Kinase A (PKA)Huse and Kuriyan, 2002The PKA structure has twomain lobes (subdomains).Huse and Kuriyan, 2002Schematized PKA structureHuse and Kuriyan, 2002The phosphate binding loop contains aconserved glycine-rich sequence motif.Phosphatebinding loop(P loop)Huse and Kuriyan, 2002αβγThe three phosphates of adenosine tri-phosphate are labeledα, β, and γPrimary sequence alignmentof protein kinase domainsHanks and Hunter, 1995The peptide substrate binds in anextended conformation across the front ofthe PKA structure.PeptidesubstrateHuse and Kuriyan, 2002Substrate (in yellow) binds acrossthe front of the structure.Huse and Kuriyan, 2002The activation loop provides a platformupon which the substrate sits.Huse and Kuriyan, 2002The activation loop (in orange) is stabilized inan extended conformation when it isphosphorylated.Huse and Kuriyan, 2002Lys72 makes contacts withthe α and β phosphate groupsHuse and Kuriyan, 2002Glu91, a residue in the αC helix, stabilizes andorients Lys72.Huse and Kuriyan, 2002Lys72αC, with Glu91extending from itConserved catalytic residuesHanks and Hunter, 1995Kinase activationFig. 12-7
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