Protein Kinases. RISK TAKING IS FOR WINNERS. Flashcards
What do protein kinases do? And what is this a fundamental step in?
Phosphorylate target proteins. It is a fundamental step in signalling and regulatory processes in eukaryotic cells.
What is the conformation like between active and inactive PKs?
There is a large conformational change between active and inactive.
What is the structure of a PK like in an active state? 5 points.
1) Bi-lobal fold 2)N-terminal domain mainly beta sheet 3)Cterminal domain mainly alpha helix 4) the 2 domains are linked by a flexible hinge which is closed in active, open in inactive 5) ATP binding site in a deep cleft between 2 lobes
What is the internal regulation of PKs like?
Conserved - outside regulation usually involves another protein
What is the gly-rich loop of PK like?
flexible and folds over ATP site, orients ATP phosphate in active conformation. Backbone NH binds to ATP phosphate, may contain inhibitory phosphorylation sites.
What is the C-helix of PK like?
a conserved glutamate E. Interacts with ATP phosphate. SOMETIMES large structural rearrangement upon activation.
What is the catalytic loop of PK like?
structure changed upon activation
What is the activation loop of PK like?
large structural rearrangement in activation - blocks binding site of other enzymes
In many protein kinases, multiple phosphates may need to be added/removed. Write this down no looking
cheat.
PKA AND G PROTEIN SIGNALLING: what is so special about a g-protein receptor and what is it known as?
g protein receptors the most abundant and 7 transmembrane helices so 7TM receptors.
What is the structural/conformational changes to the Galpha subunit when active/inactive?
GDP is bound when inactive, GTP is bound when active.
When active, what interacts directly with the GTPgamma phosphate?
3 switches.
What do 1 and 2 switch regions do with Galpha when active?
They change conformation to form H bonds to the additional phosphate of ATP.
What is the surface that Galpha touches adenyl cyclase with?
The switch region exposed by the dissociation of Gbetagamma
What is the hydrolysis of GTP to GDP enhanced by?
The binding of Galpha to its target.
