Glutamine Binding Opens the Ammonia Channel and Activates Glucosamine-6P Synthase

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 Å resolution in the presence of fructose-...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-02, Vol.281 (7), p.4404-4412
Main Authors: Mouilleron, Stéphane, Badet-Denisot, Marie-Ange, Golinelli-Pimpaneau, Béatrice
Format: Article
Language:English
Subjects:
Ammonia - metabolism
Binding Sites
Biochemistry
Biochemistry, Molecular Biology
Chemical Sciences
Enzyme Activation
Glutaminase - chemistry
Glutaminase - metabolism
Glutamine - metabolism
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - chemistry
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - metabolism
Life Sciences
Molecular biology
Organic chemistry
Structural Biology
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Summary: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 Å resolution in the presence of fructose-6P and at 2.35 Å 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 γ-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 α-amino group of Cys-1 and Asn-98 that is positioned to form the oxyanion hole, and 3) a 75° rotation of the Trp-74 indole group that opens the ammonia channel.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M511689200