Glucosamine 6-phosphate synthase

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<StructureSection load='1moq' size='350' side='right' caption='Structure of glucosamine 6-phosphate synthase complex with glucosamine-6-phosphate, sulfate and Na+ (purple) (PDB entry [[1moq]])' scene=''>
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<StructureSection load='2vf5' size='350' side='right' caption='Structure of E. coli glucosamine 6-phosphate synthase complex with glucosamine-6-phosphate (PDB entry [[2vf5]])' scene='51/516474/Cv/1'>
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== Function ==
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'''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). 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. The most potent inhibitor of G6PS is the intermediate analog amino-2-deoxy-D-glucitol 6-phosphate (ADGP). See also [[Isomerases]].
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'''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)<ref>PMID:8528769</ref>. 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]].
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== Relevance ==
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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.
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== Structural highlights ==
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The sugar binding by G6PS induces conformational change of the enzyme domains. <scene name='51/516474/Cv/5'>Active site</scene>. The <scene name='51/516474/Cv/6'>sugar binding pocket</scene> is found in the interface between the synthase and the glutaminase domains of G6PS<ref>PMID:18295797</ref>.
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</StructureSection>
==3D structures of glucosamine 6-phosphate synthase==
==3D structures of glucosamine 6-phosphate synthase==
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[[2vf4]] - EcG6PS – ''Escherichia coli''<br />
[[2vf4]] - EcG6PS – ''Escherichia coli''<br />
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[[3tbf]] – G6PS C terminal – ''Francisella tularensis''<br />
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[[1jxa]], [[2vf5]] – EcG6PS + G6P<br />
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[[1moq]], [[2vf5]] – EcG6PS + G6P<br />
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[[2j6h]] - EcG6PS + oxo-norleucine + G6P<br />
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[[1mor]], [[1jxa]] – EcG6PS + glucose 6-phosphate<br />
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[[4amv]] – EcG6PS + F6P<br />
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[[1xff]] - EcG6PS glutaminase domain + glutamate<br />
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[[1xff]] - EcG6PS glutaminase domain 1-240 + glutamate<br />
[[1xfg]] - EcG6PS glutaminase domain + glutamic hydroxamate<br />
[[1xfg]] - EcG6PS glutaminase domain + glutamic hydroxamate<br />
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[[1mos]] – EcG6PS + ADGP<br />
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[[7dnr]] – EcG6PS isomerase domain 242-609<br />
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[[2bpl]] – EcG6PS + F6P<br />
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[[1mos]] – EcG6PS isomerase domain + ADGP<br />
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[[2j6h]] - EcG6PS + oxo-norleucine + glucose 6-phosphate
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[[1moq]], [[1mor]] – EcG6PS isomerase domain + ADGP<br />
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[[2puv]] – CaG6PS isomerase domain 347-713 + uridine-2P-acetylglucosamine – ''Candida albicans''<br />
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[[2put]] – CaG6PS isomerase domain + uridine-2P-acetylglucosamine + F6P<br />
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[[2puw]] – CaG6PS isomerase domain + glucopyranose<br />
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[[2poc]] – CaG6PS isomerase domain + uridine-2P-acetylglucosamine + glucopyranose<br />
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[[3tbf]] – G6PS C terminal – ''Francisella tularensis''<br />
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

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

Drag the structure with the mouse to rotate

3D 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

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

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Michal Harel, Alexander Berchansky

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