Department of Biomedicine, University of Bergen, Bergen, Norway.
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Nat Commun. 2021 Mar 12;12(1):1631. doi: 10.1038/s41467-021-21307-z.
Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host's NAD pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.
烟酰胺腺嘌呤二核苷酸（NAD）是细胞生物能量学和信号转导的关键分子。各种细菌病原体将 NAD 酶释放到宿主细胞中，耗尽宿主的 NAD 池，从而导致细胞迅速死亡。在这里，我们报告了真菌表面 NAD 酶的鉴定，如病原体烟曲霉和腐生菌粗糙脉孢菌。这些酶含有结核坏死毒素（TNT）结构域，主要存在于致病性物种中。烟曲霉蛋白同源二聚体的 1.6Å X 射线结构揭示了独特的性质，包括 N 连接糖基化和钙结合位点，其占据状态调节活性。与底物类似物的复合物结构表明了一种与已知的 NAD 酶、ADP-核糖环化酶和转移酶不同的催化机制。我们提出，真菌 NAD 酶可能在与宿主或竞争微生物相互作用过程中具有优势。
