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Science 13 September 1996:
Vol. 273. no. 5281, pp. 1539 - 1541
DOI: 10.1126/science.273.5281.1539
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Reports

A Protein Phosphorylation Switch at the Conserved Allosteric Site in GP

Kai Lin, Virginia L. Rath, Shirleko C. Dai, Robert J. Fletterick, * Peter K. Hwang *

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.

K. Lin, S. C. Dai, R. J. Fletterick, P. K. Hwang, Department of Biochemistry and Biophysics, University of California at San Francisco, 513 Parnassus, San Francisco, CA 94143, USA.
V. L. Rath, Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
*   To whom correspondence should be addressed.


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