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| | <StructureSection load='4bma' size='340' side='right'caption='[[4bma]], [[Resolution|resolution]] 2.08Å' scene=''> | | <StructureSection load='4bma' size='340' side='right'caption='[[4bma]], [[Resolution|resolution]] 2.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bma]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BMA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bma]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BMA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_diphosphorylase UDP-N-acetylglucosamine diphosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.23 2.7.7.23] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bma OCA], [http://pdbe.org/4bma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bma RCSB], [http://www.ebi.ac.uk/pdbsum/4bma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bma ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bma OCA], [https://pdbe.org/4bma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bma RCSB], [https://www.ebi.ac.uk/pdbsum/4bma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bma ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q4WAR0_ASPFU Q4WAR0_ASPFU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Aspergillus fumigatus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: UDP-N-acetylglucosamine diphosphorylase]]
| + | [[Category: Fang W]] |
| - | [[Category: Fang, W]] | + | [[Category: HurtadoGuerrero R]] |
| - | [[Category: HurtadoGuerrero, R]] | + | [[Category: Raimi OG]] |
| - | [[Category: Raimi, O G]] | + | [[Category: VanAalten DMF]] |
| - | [[Category: VanAalten, D M.F]] | + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Udp-glcnac biosynthesis pathway]]
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| Structural highlights
Function
Q4WAR0_ASPFU
Publication Abstract from PubMed
The sugar nucleotide UDP-N-acetylglucosamine (UDP-GlcNAc) is an essential metabolite in both prokaryotes and eukaryotes. In fungi, it is the precursor for the synthesis of chitin, an essential component of the fungal cell wall. UDP-N-acetylglucosamine pyrophosphorylase (UAP) is the final enzyme in eukaryotic UDP-GlcNAc biosynthesis, converting UTP and N-acetylglucosamine-1-phosphate (GlcNAc-1P) to UDP-GlcNAc. As such, this enzyme may provide an attractive target against pathogenic fungi. Here, we demonstrate that the fungal pathogen Aspergillus fumigatus possesses an active UAP (AfUAP1) that shows selectivity for GlcNAc-1P as the phosphosugar substrate. A conditional mutant, constructed by replacing the native promoter of the A. fumigatus uap1 gene with the Aspergillus nidulans alcA promoter, revealed that uap1 is essential for cell survival and important for cell wall synthesis and morphogenesis. The crystal structure of AfUAP1 was determined and revealed exploitable differences in the active site compared to the human enzyme. Thus AfUAP1 could represent a novel antifungal target and this work will assist the future discovery of small molecule inhibitors against this enzyme.
Genetic and structural validation of Aspergillus fumigatus UDP-N-acetylglucosamine pyrophosphorylase as an antifungal target.,Fang W, Du T, Raimi OG, Hurtado-Guerrero R, Urbaniak MD, Ibrahim AF, Ferguson MA, Jin C, van Aalten DM Mol Microbiol. 2013 Jun 10. doi: 10.1111/mmi.12290. PMID:23750903[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fang W, Du T, Raimi OG, Hurtado-Guerrero R, Urbaniak MD, Ibrahim AF, Ferguson MA, Jin C, van Aalten DM. Genetic and structural validation of Aspergillus fumigatus UDP-N-acetylglucosamine pyrophosphorylase as an antifungal target. Mol Microbiol. 2013 Jun 10. doi: 10.1111/mmi.12290. PMID:23750903 doi:10.1111/mmi.12290
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