4BMA

structural of Aspergillus fumigatus UDP-N-acetylglucosamine pyrophosphorylase

4BMA の概要

• エントリーDOI: 10.2210/pdb4bma/pdb
• 分子名称: UDP-N-ACETYLGLUCOSAMINE PYROPHOSPHORYLASE, GLYCEROL (3 entities in total)
• 機能のキーワード: transferase, udp-glcnac biosynthesis pathway
• 由来する生物種: ASPERGILLUS FUMIGATUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113679.27

構造登録者

Fang, W.,Raimi, O.G.,HurtadoGuerrero, R.,vanAalten, D.M.F. (登録日: 2013-05-07, 公開日: 2013-05-15, 最終更新日: 2023-12-20)

主引用文献

Fang, W.,Du, T.,Raimi, O.G.,Hurtado-Guerrero, R.,Urbaniak, M.D.,Ibrahim, A.F.,Ferguson, M.A.,Jin, C.,Van Aalten, D.M.
Genetic and Structural Validation of Aspergillus Fumigatus Udp-N-Acetylglucosamine Pyrophosphorylase as an Antifungal Target.
Mol.Microbiol., 89:479-, 2013

PubMed Abstract: 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.

PubMed: 23750903
DOI: 10.1111/MMI.12290

実験手法

X-RAY DIFFRACTION (2.08 Å)