| 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. Active site. The sugar binding pocket is found in the interface between the synthase and the glutaminase domains of G6PS[2].
- ↑ 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
- ↑ 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
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3D structures of glucosamine 6-phosphate synthase
Updated on 14-March-2023
Isomerases - EcG6PS – Escherichia coli
1jxa, 2vf5 – EcG6PS + G6P
2j6h - EcG6PS + oxo-norleucine + G6P
4amv – EcG6PS + F6P
1xff - EcG6PS glutaminase domain 1-240 + glutamate
1xfg - EcG6PS glutaminase domain + glutamic hydroxamate
7dnr – EcG6PS isomerase domain 242-609
1mos – EcG6PS isomerase domain + ADGP
1moq, 1mor – EcG6PS isomerase domain + ADGP
2puv – CaG6PS isomerase domain 347-713 + uridine-2P-acetylglucosamine – Candida albicans
2put – CaG6PS isomerase domain + uridine-2P-acetylglucosamine + F6P
2puw – CaG6PS isomerase domain + glucopyranose
2poc – CaG6PS isomerase domain + uridine-2P-acetylglucosamine + glucopyranose
3tbf – G6PS C terminal – Francisella tularensis
References
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