Synergistic effects of substrate-induced conformational changes in phosphoglycerate kinase activation

Nature. 1997 Jan 16;385(6613):275-8. doi: 10.1038/385275a0.


Phosphoglycerate kinase (PGK), a key enzyme in glycolysis, catalyses the transfer of a phosphoryl-group from 1,3-bisphosphoglycerate to ADP to form 3-phosphoglycerate and ATP. Despite extensive kinetic and structural investigations over more than two decades, the conformation assumed by this enzyme during catalysis remained unknown. Here we present the 2.8 A crystal structure of a ternary complex of PGK from Trypanosoma brucei, the causative agent of sleeping sickness. This structure determination relied on a procedure in which fragments containing less than 10% of the scattering mass were successively positioned in the unit cell to obtain phases. The PGK ternary complex exhibits a dramatic closing of the large cleft between the two domains seen in all previous studies, thereby bringing the two ligands, 3-phosphoglycerate and ADP into close proximity. Our results demonstrate that PGK is a hinge-bending enzyme, reveal a novel mechanism in which substrate-induced effects combine synergistically to induce major conformational changes and, to our knowledge, afford the first observation of the PGK active site in a catalytic conformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Allosteric Regulation
  • Animals
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Enzyme Activation
  • Escherichia coli
  • Glyceric Acids / metabolism
  • Models, Molecular
  • Phosphoglycerate Kinase / chemistry*
  • Phosphoglycerate Kinase / metabolism
  • Protein Conformation*
  • Recombinant Proteins / chemistry
  • Trypanosoma brucei brucei / enzymology


  • Glyceric Acids
  • Recombinant Proteins
  • Adenosine Diphosphate
  • 3-phosphoglycerate
  • Phosphoglycerate Kinase