Glucosamine 6-phosphate synthase

Function

Glucosamine 6-phosphate synthase (G6PS) catalyzes the first step in the biosynthesis of UDP-GlcNAc. G6PS converts fructose-6-phosphate (F6P) and glutamine to glucosamine-6-phosphate (G6P)^[1]. G6PS consists of two domains which catalyze two reactions. The N-terminal glutaminase domain (E.coli residues 2-239) which catalyzes the hydrolysis of glutamine to glutamate and ammonia which is transferred to F6P and the C-terminal synthase domain (E.coli residues 248-end) which catalyzes the isomerization of F6P from ketose to aldose. The most potent inhibitor of G6PS is the intermediate analog amino-2-deoxy-D-glucitol 6-phosphate (ADGP). See also Isomerases.

Relevance

N-acetylglucosamine is an essential building block of chitin which comprises the bacterial and fungal cell wall. Hence, G6PS is a target to anti-bacterial and anti-fungal agents.

Structural highlights

The sugar binding by G6PS induces conformational change of the enzyme domains. . The is found in the interface between the synthase and the glutaminase domains of G6PS^[2].