MECHANISTIC INVESTIGATIONS ON GLUCOSAMINE-6-PHOSPHATE SYNTHASE

The goal of this article is to review the state of our knowledge on gl ucosamine-6-phosphate synthase (GlmS) on the basis of results obtained over the past few years. GlmS from Escherichia coli catalyses the syn thesis 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. Che mical modification, protein sequence comparisons, and site-directed mu tagenesis demonstrate the intervention of at least three catalytic res idues, cysteine 1, aspartate 123, and lysine 603, in the overall mecha nism. Both the elucidation of the mechanism of inhibition of this enzy me using a naturally occurring inhibitor and related synthetic compoun ds, and its antifungal properties, demonstrate GlmS as a promising tar get in drug development.