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Printable Handouts
Navigable Slide Index
- Introduction
- The human kinome
- PKA sequence
- PKA and Src define conserved subdomains
- cAMP is an ancient signaling molecule
- cAMP dependent protein kinase
- Outline
- PKI is a highly specific PKA inhibitor
- PKI structure
- Crystallized structure of PKI
- What do we learn from the sequence of PKI?
- Cross linked residues at active site
- N lobe
- Glycine-rich loop
- The catalytic machinery (1)
- The catalytic machinery (2)
- Prototype for catalysis
- Conserved active site residues
- Opening and closing of the active site cleft
- Close-up on active site
- Inhibitor peptide docks into active site (1)
- Inhibitor peptide docks into active site (2)
- The super family of kinases
- Correlating secondary structure and sequence
- Subdomains are conserved
- What can we learn from the structural kinome?
- Anatomy of a kinase
- Analysis of protein kinase core by LSP
- LSP
- The assembly of a hydrophobic spine
- Regulatory spine
- Second hydrophobic motif - catalytic spine
- The kinase hydrophobic core
- F-Helix as a scaffold
- Insulin receptor kinase
- PKB and Akt
- Kinase activation
- Why is this phosphate so important?
- Phosphorylation of Thr197
- Allostery and regulation by phosphorylation in EPK
- Importance of one phosphate
- Phosphorylation of activation segment
- Is phosphorylation of activation loop sufficient?
- Optimizing the N-lobe for catalysis (1)
- Protein kinase family members
- PKA catalytic subunit
- C-tail
- The C-tail of PKA
- Cis regulatory element
- Optimizing the N-lobe for catalysis (2)
- Optimizing the N-lobe for catalysis (3)
- Optimizing the N-lobe for catalysis (4)
- Priming of the C-lobe and the N-lobe for catalysis
- Future challenges
- Questions about inhibition and activation
- PKA architecture
- The surface of PKA
- The regulatory subunits (1)
- Extended complex interface
- Conformational dynamics of the regulatory subunit
- Conformational changes in RI-alpha
- A-Kinase Anchoring Proteins (AKAPs)
- Regulation and localization of PKA
- The regulatory subunits (2)
- Integration of signaling by PKA
- Docking domain of RI-alpha bound to DAKAP2
- PKA proteome
- PKA signaling
- Acknowledgements
Topics Covered
- Overview of protein kinase structure and function using PKA as a prototype for this enzyme superfamily
- What we have learned from the overall structural kinome
- Comparison of many protein kinases
- Eukaryotic protein kinase regulation
- Elucidation of general rules of architecture
- Illustration of how PKA is regulated by cAMP and how it is localized to specific macromolecular complexes through scaffold proteins
Talk Citation
Taylor, S. (2010, November 30). Protein kinase structure, function and regulation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 12, 2019, from https://hstalks.com/bs/1886/.Publication History
Financial Disclosures
- Prof. Susan Taylor has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Protein kinase structure, function and regulation
Published on November 30, 2010
45 min