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  • The EMBO Journal (2004) 23, 3196 - 3205
  • doi:10.1038/sj.emboj.7600324

Published online: 22 July 2004

Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation

Alejandro Buschiazzo1, Juan E Ugalde2, Marcelo E Guerin1, William Shepard3, Rodolfo A Ugalde2 and Pedro M Alzari1

  1. Unité de Biochimie Structurale, URA 2185 CNRS, Institut Pasteur, Paris, France
  2. Instituto de Investigaciones Biotecnológicas, Universidad de General San Martín and CONICET, CC 30, San Martín, Argentina
  3. European Synchrotron Radiation Facility, Grenoble, France

Correspondence to:

Pedro M Alzari, Unité de Biochimie Structurale, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France. Tel.: +33 1 45 68 8607; Fax: +33 1 45 68 8604; E-mail: alzari@pasteur.fr

Received 17 March 2004; Accepted 21 June 2004

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.

  • Keywords:

    • glycogen,
    • glycosyltransferase,
    • starch,
    • 3D structure,
    • X-ray crystallography