Figure 1.

Binding of AMP to the γ1 subunit. Stick presentation of the three AMP molecules (green carbon atoms) and key AMP-binding residues of AMPK (cyan carbon atoms). Oxygen is colored in red, nitrogen in blue, and phosphorus in orange. The phosphate groups of the 3 AMP molecules are coordinately bound by a set of charged amino acids, whereas the ribose and adenine rings face away from each other and are bound by CBS-specific residues. Mutations of the indicated adenine-binding residues therefore selectively block AMP binding to individual CBS sites. Note that the adenine-binding mutations at CBS3 and CBS4 are each sufficient, even at the high concentration of adenine nucleotides in cells, to completely abolish AMPK activation by AMP without affecting AMPK catalytic activity in the absence of AMP (18).