Structural Studies on the Synchronization of Catalytic Centers in Glutamate Synthase

J Biol Chem. 2002 Jul 5;277(27):24579-83. doi: 10.1074/jbc.M202541200. Epub 2002 Apr 19.


The complex iron-sulfur flavoprotein glutamate synthase (GltS) plays a prominent role in ammonia assimilation in bacteria, yeasts, and plants. GltS catalyzes the formation of two molecules of l-glutamate from 2-oxoglutarate and l-glutamine via intramolecular channeling of ammonia. GltS has the impressive ability of synchronizing its distinct catalytic centers to avoid wasteful consumption of l-glutamine. We have determined the crystal structure of the ferredoxin-dependent GltS in several ligation and redox states. The structures reveal the crucial elements in the synchronization between the glutaminase site and the 2-iminoglutarate reduction site. The structural data combined with the catalytic properties of GltS indicate that binding of ferredoxin and 2-oxoglutarate to the FMN-binding domain of GltS induce a conformational change in the loop connecting the two catalytic centers. The rearrangement induces a shift in the catalytic elements of the amidotransferase domain, such that it becomes activated. This machinery, over a distance of more than 30 A, controls the ability of the enzyme to bind and hydrolyze the ammonia-donating substrate l-glutamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / chemistry*
  • Amino Acid Oxidoreductases / metabolism
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyanobacteria / enzymology
  • Ferredoxins / metabolism
  • Glutamate Synthase / chemistry*
  • Glutamate Synthase / metabolism
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Conformation


  • Ferredoxins
  • Amino Acid Oxidoreductases
  • Glutamate Synthase
  • glutamate synthase (ferredoxin)