A protein phosphorylation switch at the conserved allosteric site in GP.
A phosphorylation-initiated mechanism of local protein refolding activates yeast glycogen phosphorylase (GP). Refolding of the phosphorylated amino-terminus was shown to create a hydrophobic cluster that wedges into the subunit interface of the enzyme to trigger activation. The phosphorylated threonine is buried in the allosteric site. The mechanism implicates glucose 6-phosphate, the allosteric inhibitor, in facilitating dephosphorylation by dislodging the buried covalent phosphate through binding competition. Thus, protein phosphorylation-dephosphorylation may also be controlled through regulation of the accessibility of the phosphorylation site to kinases and phosphatases. In mammalian glycogen phosphorylase, phosphorylation occurs at a distinct locus. The corresponding allosteric site binds a ligand activator, adenosine monophosphate, which triggers activation by a mechanism analogous to that of phosphorylation in the yeast enzyme.
Lin
K
K
Department of Biochemistry and Biophysics, University of California at San Francisco, 513 Parnassus, San Francisco, CA 94143, USA.
Rath
V L
VL
Dai
S C
SC
Fletterick
R J
RJ
Hwang
P K
PK
D000249:Adenosine Monophosphate / Q000378:metabolism; D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D006005:Phosphorylases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D004791:Enzyme Inhibitors; D005958:Glucosephosphates; D000249:Adenosine Monophosphate; D019298:Glucose-6-Phosphate; D006005:Phosphorylases