MECHANISTIC INVESTIGATIONS ON GLUCOSAMINE-6-PHOSPHATE SYNTHASE

The goal of this article is to review the state of our knowledge on glucosamine-6-phosphate synthase (GlmS) on the basis of results obtained over the past few years. GlmS from Escherichia coli catalyses the synthesis of glucosamine-6P from fructose-6P and L-glutamine. The enzyme has two domains, one of which is responsible for the formal generation of ammonia from glutamine, and the other for the condensation of this glutamine with fructose-6P to generate 2-amino-2-deoxy-D-glucose. Chemical modification, protein sequence comparisons, and site-directed mutagenesis demonstrate the intervention of at least three catalytic residues, cysteine 1, aspartate 123, and lysine 603, in the overall mechanism. Both the elucidation of the mechanism of inhibition of this enzyme using a naturally occurring inhibitor and related synthetic compounds, and its antifungal properties, demonstrate GlmS as a promising target in drug development.