Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.
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.
Douangamath
Alice
A
EMBL Hamburg Outstation c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.
Walker
Martina
M
Beismann-Driemeyer
Silke
S
Vega-Fernandez
M Cristina
MC
Sterner
Reinhard
R
Wilmanns
Matthias
M
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*
D046911:Macromolecular Substances; D021122:Protein Subunits; D000641:Ammonia; C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases