Conforma5onal changes does this cause cdk2 ac5va5on

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Unformatted text preview: One Ac5ve Conforma5on to Rule Them All …but different inac5ve conforma5ons. In addi5on to relieving inhibi5ng factors, phosphoryla5on on the ac5va5on loop is almost always required to stabilize the ac5ve conforma5on Phosphatases remove the ac5va5on loop phosphate, turning the kinase “off” Kinase Ac5va5on Example: Cdk2 Cdk2 ac5va5on movie •  You will see various structures and interpola5ons between them •  ATP is bound in each of these but is only shown when the “mo5on” stops •  First, Cyclin A will bind •  Then, Thr160 will be phosphorylated •  Conforma5on will shiX to bind pep5de substrate •  Lastly, the pep5de substrate will be bound, in posi5on to accept phosphate from ATP •  What distant conforma5onal changes does this cause? Cdk2 ac5va5on movie Protein Kinase B (AKT) Ac5va5on Movie •  Three events required for full ac5va5on: –  Phosphoryla5on of ac5va5on (“DFG”) loop (Red) –  Phosphoryla5on of Hydrophobic Mo5f on C- term –  Binding of Hydrophobic Mo5f to its pocket (Green) •  This posi5ons and rigidifies the αC helix Phosphoryla5on of PKB (Akt)'s Ac5va5on Loop Stabilizes Ac5...
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