title: Channeling of ammonia in glucosamine-6-phosphate synthase.
abstract: Glucosamine-6-phosphate synthase catalyses the first and rate-limiting step in hexosamine metabolism, converting fructose 6-phosphate into glucosamine 6-phosphate in the presence of glutamine. The crystal structure of the Escherichia coli enzyme reveals the domain organisation of the homodimeric molecule. The 18 A hydrophobic channel sequestered from the solvent connects the glutaminase and isomerase active sites, and provides a means of ammonia transfer from glutamine to sugar phosphate. The C-terminal decapeptide sandwiched between the two domains plays a central role in the transfer. Based on the structure, a mechanism of enzyme action and self-regulation is proposed. It involves large domain movements triggered by substrate binding that lead to the formation of the channel.
authors.affiliation: European Molecular Biology Laboratory, Notkestr. 85, D-22603 Hamburg, Germany. alexey@carb.inst.gov
authors.forename: A
authors.initials: A
authors.lastname: Teplyakov
authors.forename: G
authors.initials: G
authors.lastname: Obmolova
authors.forename: B
authors.initials: B
authors.lastname: Badet
authors.forename: M A
authors.initials: MA
authors.lastname: Badet-Denisot
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology*; D005972:Glutaminase / Q000737:chemistry / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry* / Q000378:metabolism*; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012997:Solvents; D013329:Structure-Activity Relationship
chemical_list: D009097:Multienzyme Complexes; D012997:Solvents; D005973:Glutamine; D000641:Ammonia; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005972:Glutaminase; D007535:Isomerases; D009584:Nitrogen