AMPK
fuel sensor of the cell
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Alpha Subunit - missing C terminal flexible loop (471-523)
The alpha subunit is the catalytic
subunit. When phosphorylated on Thr 172, its activity increases
100X.
Add Beta Subunit
(Green)
The
carboxy-terminal domain is shown
Add Gamma Subunit
(Blue)
The gamma subunit binds AXP (AMP,
ADP, ATP) at 4 possible binding sites. Site 2 is unoccupied,
site 4 has an AMP seemingly always bound. Sites 1 binds all AXP
with similarly high affinity (50x greater than site 3) and
allosterically increases the activity of the phosphorylated from 2-5X.
Occupancy of site 3 affects dephosphorylation of T172.
Add AMP (spacefill)
AMP is shown
bound to site 3 and 4.
Add Staurosporine (gray, spacefill)
Staurosporine is a high affinity competitive
inhibitor of ATP binding to the catalytic site of many protein kinases
Add pThr
(A172 and
A377 (spacefill)
When AMP is bound to site 3, pThr 172
can't be dephosphorylated. If ADP rises in the cell, it
displaces ATP at site 3 and also prevents dephosphorylation of
pT172.
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