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 catalyzes two reactions. The first is the hydrolysis of glutamine to glutamate and ammonia which is transferred to F6P and the second is 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. The sugar binding pocket is found in the interface between the synthase and the glutaminase domains of G6PS^[2].

3D structures of glucosamine 6-phosphate synthase

Updated on 07-March-2016

2vf4 - EcG6PS – Escherichia coli

3tbf – G6PS C terminal – Francisella tularensis
1moq, 2vf5 – EcG6PS + G6P
1mor, 1jxa – EcG6PS + glucose 6-phosphate
1xff - EcG6PS glutaminase domain + glutamate
1xfg - EcG6PS glutaminase domain + glutamic hydroxamate
1mos – EcG6PS + ADGP
2bpl – EcG6PS + F6P
2j6h - EcG6PS + oxo-norleucine + glucose 6-phosphate

References

1. ↑ White SH, Wimley WC, Selsted ME. Structure, function, and membrane integration of defensins. Curr Opin Struct Biol. 1995 Aug;5(4):521-7. PMID:8528769
2. ↑ Mouilleron S, Badet-Denisot MA, Golinelli-Pimpaneau B. Ordering of C-terminal loop and glutaminase domains of glucosamine-6-phosphate synthase promotes sugar ring opening and formation of the ammonia channel. J Mol Biol. 2008 Apr 4;377(4):1174-85. Epub 2008 Feb 4. PMID:18295797 doi:10.1016/j.jmb.2008.01.077