Channeling of ammonia in glucosamine-6-phosphate synthase

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 Angstrom 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. (C) 2001 Academic Press.