Science, Vol 254, Issue 5036, 1367-1371
Copyright © 1991 by American Association for the Advancement of Science
Structural basis for the activation of glycogen phosphorylase b by adenosine monophosphate
Sprang SR,
SG Withers,
EJ Goldsmith,
RJ Fletterick,
and
NB Madsen
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9050.
The three-dimensional structure of the activated state of glycogen phosphorylase (GP) as induced by adenosine monophosphate (AMP) has been determined from crystals of pyridoxalpyrophosphoryl-GP. The same quaternary changes relative to the inactive conformation as those induced by phosphorylation are induced by AMP, although the two regulatory signals function through different local structural mechanisms. Moreover, previous descriptions of the phosphorylase active state have been extended by demonstrating that, on activation, the amino- and carboxyl-terminal domains of GP rotate apart by 5 degrees, thereby increasing access of substrates to the catalytic site. The structure also reveals previously unobserved interactions with the nucleotide that accounts for the specificity of the nucleotide binding site for AMP in preference to inosine monophosphate.
