AMPK

fuel sensor of the cell

HTML 5 version (does not require Java; downloads and moves slowly)

I. Introduction

For more information see Biochemistry Online: Chapter 9C - Signal Transduction - Kinases and Phosphatases

II. General Structure

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.