Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex

Structure. 2002 Feb;10(2):185-93. doi: 10.1016/s0969-2126(02)00702-5.

Abstract

Since reactive ammonia is not available under physiological conditions, glutamine is used as a source for the incorporation of nitrogen in a number of metabolic pathway intermediates. The heterodimeric ImGP synthase that links histidine and purine biosynthesis belongs to the family of glutamine amidotransferases in which the glutaminase activity is coupled with a subsequent synthase activity specific for each member of the enzyme family. Its X-ray structure from the hyperthermophile Thermotoga maritima shows that the glutaminase subunit is associated with the N-terminal face of the (beta alpha)(8) barrel cyclase subunit. The complex reveals a putative tunnel for the transfer of ammonia over a distance of 25 A. Although ammonia tunneling has been reported for glutamine amidotransferases, the ImGP synthase has evolved a novel mechanism, which extends the known functional properties of the versatile (beta alpha)(8) barrel fold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aminohydrolases / chemistry*
  • Aminohydrolases / metabolism*
  • Ammonia / metabolism*
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Subunits
  • Static Electricity
  • Structure-Activity Relationship
  • Thermotoga maritima / enzymology*

Substances

  • Macromolecular Substances
  • Protein Subunits
  • Ammonia
  • imidazole glycerol phosphate synthase
  • Aminohydrolases

Associated data

  • PDB/1GPW
  • PDB/1K9V