title: Dynamics of glucosamine-6-phosphate synthase catalysis.
abstract: Glucosamine-6P synthase, which catalyzes glucosamine-6P synthesis from fructose-6P and glutamine, channels ammonia over 18Å between its glutaminase and synthase active sites. The crystal structures of the full-length Escherichia coli enzyme have been determined alone, in complex with the first bound substrate, fructose-6P, in the presence of fructose-6P and a glutamine analog, and in the presence of the glucosamine-6P product. These structures represent snapshots of reaction intermediates, and their comparison sheds light on the dynamics of catalysis. Upon fructose-6P binding, the C-terminal loop and the glutaminase domains get ordered, leading to the closure of the synthase site, the opening of the sugar ring and the formation of a "closed" ammonia channel. Then, glutamine binding leads to the closure of the Q-loop to protect the glutaminase site, the activation of the catalytic residues involved in glutamine hydrolysis, the swing of the side chain of Trp74, which allows the communication between the two active sites through an "open" channel, and the rotation of the glutaminase domains relative to the synthase domains dimer. Therefore, binding of the substrates at the appropriate reaction time is responsible for the formation and opening of the ammonia channel and for the activation of the enzyme glutaminase function.
authors: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, France. stephane.mouilleron@cancer.org.uk
authors: Stéphane
authors: S
authors: Mouilleron
authors: Marie-Ange
authors: MA
authors: Badet-Denisot
authors: Bernard
authors: B
authors: Badet
authors: Béatrice
authors: B
authors: Golinelli-Pimpaneau
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)