title: Glutamine binding opens the ammonia channel and activates glucosamine-6P synthase.
abstract: Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site. X-ray structures of glucosamine-6P synthase have been determined at 2.05 Angstroms resolution in the presence of fructose-6P and at 2.35 Angstroms resolution in the presence of fructose-6P and 6-diazo-5-oxo-L-norleucine, a glutamine affinity analog that covalently modifies the N-terminal catalytic cysteine, therefore mimicking the gamma-glutamyl-thioester intermediate formed during hydrolysis of glutamine. The fixation of the glutamine analog activates the enzyme through several major structural changes: 1) the closure of a loop to shield the glutaminase site accompanied by significant domain hinging, 2) the activation of catalytic residues involved in glutamine hydrolysis, i.e. the alpha-amino group of Cys-1 and Asn-98 that is positioned to form the oxyanion hole, and 3) a 75 degrees rotation of the Trp-74 indole group that opens the ammonia channel.
authors.affiliation: Laboratoire d'Enzymologie et de Biochimie Structurales, Unite Propre de Recherche 9063, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouilleron
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Badet-Denisot
authors.forename: Béatrice
authors.initials: B
authors.lastname: Golinelli-Pimpaneau
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D001665:Binding Sites; D004789:Enzyme Activation; D005972:Glutaminase / Q000737:chemistry / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005973:Glutamine; D000641:Ammonia; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005972:Glutaminase