2uv5

Structural highlights

Function

AAKG1_HUMAN AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.^[1]

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• AMP-activated protein kinase 3D structures

References

1. ↑ Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N, Tam S, Kemp BE. AMPK is a direct adenylate charge-regulated protein kinase. Science. 2011 Jun 17;332(6036):1433-5. doi: 10.1126/science.1200094. PMID:21680840 doi:http://dx.doi.org/10.1126/science.1200094
2. ↑ Day P, Sharff A, Parra L, Cleasby A, Williams M, Horer S, Nar H, Redemann N, Tickle I, Yon J. Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK in complex with AMP and ZMP. Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):587-96. Epub 2007, Apr 21. PMID:17452784 doi:S0907444907009110