Involvement of the C terminus in intramolecular nitrogen channeling in glucosamine 6-phosphate synthase: evidence from a 1.6 A crystal structure of the isomerase domain

Structure. 1998 Aug 15;6(8):1047-55. doi: 10.1016/s0969-2126(98)00105-1.


Background: Glucosamine 6-phosphate synthase (GlmS) catalyses the first step in hexosamine metabolism, converting fructose-6P (6 phosphate) into glucosamine-6P using glutamine as a nitrogen source. GlmS is a bienzyme complex consisting of two domains that catalyse glutamine hydrolysis and sugar-phosphate isomerisation, respectively. Knowledge of the three-dimensional structure of GlmS is essential for understanding the general principles of catalysis by ketol isomerases and the mechanism of nitrogen transfer in glutamine amidotransferases.

Results: The crystal structure of the isomerase domain of the Escherichia coli GlmS with the reaction product, glucosamine-6P, has been determined at 1.57 A resolution. It is comprised of two topologically identical subdomains, each of which is dominated by a nucleotide-binding motif of a flavodoxin type. The catalytic site is assembled by dimerisation of the protein.

Conclusions: The isomerase active site of GlmS seems to be the result of evolution through gene duplication and subsequent dimerisation. Isomerisation of fructose-6P is likely to involve the formation of a Schiff base with Lys603 of the enzyme, the ring-opening step catalysed by His504, and the proton transfer from C1 to C2 of the substrate effected by Glu488. The highly conserved C-terminal fragment of the chain may play a key role in substrate binding, catalysis and communication with the glutaminase domain. The corresponding sequence pattern DXPXXLAK[SC]VT (in single-letter amino-acid code, where X is any amino acid and letters in brackets indicate that either serine or cysteine may take this position) may be considered as a fingerprint of GlmS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / physiology
  • Dimerization
  • Escherichia coli / enzymology*
  • Fructosephosphates / metabolism
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / chemistry*
  • Hydrogen Bonding
  • Hydrolases / chemistry
  • Isomerases / chemistry
  • Isomerism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary


  • Fructosephosphates
  • fructose-6-phosphate
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
  • Hydrolases
  • Isomerases

Associated data

  • PDB/1MOQ