Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
Organ / tissue: cell wall
NCBI PubMed ID: 23750903Publication DOI: 10.1111/mmi.12290Journal NLM ID: 8712028Publisher: Blackwell Publishing
Correspondence: van Aalten DM <dmfvanaalten
dundee.ac.uk>; Jin C <jinc
sun.im.ac.cn>
Institutions: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK, Division of Biological Chemistry and Drug Discovery College of Life Sciences, University of Dundee, Dundee, UK, The College of Life Sciences Cloning Team, College of Life Sciences, University of Dundee, Dundee, UK
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 with 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.
Structure type: structural motif or average structure
Location inside paper: p. 479, column 2, paragraph 2
Trivial name: chitin
Compound class: cell wall polysaccharide, glucan
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_153212,IEDB_241099,IEDB_423114,IEDB_423150,SB_74,SB_85
Methods: PCR, SDS-PAGE, genetic methods, electron microscopy, fluorescence microscopy
Enzymes that release or process the structure: AfUAP1, CaUAP1, HsUAP1
Related record ID(s): 42643, 42648, 44855, 44856, 44877, 44889, 44899, 44913, 44915, 44916, 44917, 44923, 44925, 44940
NCBI Taxonomy refs (TaxIDs): 746128Reference(s) to other database(s): GTC:G97099AY
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error