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].

Structure of E. coli glucosamine 6-phosphate synthase complex with glucosamine-6-phosphate (PDB entry 2vf5)

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3D structures of glucosamine 6-phosphate synthase3D structures of glucosamine 6-phosphate synthase

Updated on 14-March-2023

2vf4 - 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

ReferencesReferences

↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[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

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