title: Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.
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.
authors.affiliation: EMBL Hamburg Outstation c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Douangamath
authors.forename: Martina
authors.initials: M
authors.lastname: Walker
authors.forename: Silke
authors.initials: S
authors.lastname: Beismann-Driemeyer
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Vega-Fernandez
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sterner
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000595:Amino Acid Sequence; D000619:Aminohydrolases / Q000737:chemistry* / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D055672:Static Electricity; D013329:Structure-Activity Relationship; D020124:Thermotoga maritima / Q000201:enzymology*
chemical_list: D046911:Macromolecular Substances; D021122:Protein Subunits; D000641:Ammonia; C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases