Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation.
Glycogen and starch are the major readily accessible energy storage compounds in nearly all living organisms. Glycogen is a very large branched glucose homopolymer containing about 90% alpha-1,4-glucosidic linkages and 10% alpha-1,6 linkages. Its synthesis and degradation constitute central pathways in the metabolism of living cells regulating a global carbon/energy buffer compartment. Glycogen biosynthesis involves the action of several enzymes among which glycogen synthase catalyzes the synthesis of the alpha-1,4-glucose backbone. We now report the first crystal structure of glycogen synthase in the presence and absence of adenosine diphosphate. The overall fold and the active site architecture of the protein are remarkably similar to those of glycogen phosphorylase, indicating a common catalytic mechanism and comparable substrate-binding properties. In contrast to glycogen phosphorylase, glycogen synthase has a much wider catalytic cleft, which is predicted to undergo an important interdomain 'closure' movement during the catalytic cycle. The structures also provide useful hints to shed light on the allosteric regulation mechanisms of yeast/mammalian glycogen synthases.
Unité de Biochimie Structurale, URA 2185 CNRS, Institut Pasteur, Paris, France.
Alejandro
A
Buschiazzo
Juan E
JE
Ugalde
Marcelo E
ME
Guerin
William
W
Shepard
Rodolfo A
RA
Ugalde
Pedro M
PM
Alzari
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D016960:Agrobacterium tumefaciens / Q000201:enzymology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006003:Glycogen / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000737:chemistry / Q000378:metabolism; D006006:Glycogen Synthase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein
D000244:Adenosine Diphosphate; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase