Aspergillus fumigatus is a saprophytic ubiquitous fungus whose spores can trigger reactions such as allergic bronchopulmonary aspergillosis or the fatal invasive pulmonary aspergillosis. To survive in the lungs, the fungus must adapt to a hypoxic and nutritionally restrictive environment, exploiting the limited availability of aromatic amino acids (AAAs) in the best possible way, as mammals do not synthesize them. A key enzyme for AAAs catabolism in A. fumigatus is AroH, a pyridoxal 5′-phosphate-dependent aromatic aminotransferase. AroH was recently shown to display a broad substrate specificity, accepting L-kynurenine and α-aminoadipate as amino donors besides AAAs. Given its pivotal role in the adaptability of the fungus to nutrient conditions, AroH represents a potential target for the development of innovative therapies against A. fumigatus-related diseases. We have solved the crystal structure of Af-AroH at 2.4 Å resolution and gained new insight into the dynamics of the enzyme's active site, which appears to be crucial for the design of inhibitors. The conformational plasticity of the active site pocket is probably linked to the wide substrate specificity of AroH.

中文翻译：

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烟曲霉 AroH 的晶体结构，一种芳香族氨基酸氨基转移酶

烟曲霉是一种无处不在的腐生真菌，其孢子可引发过敏性支气管肺曲霉病或致命的侵袭性肺曲霉病等反应。为了在肺部生存，真菌必须适应缺氧和营养受限的环境，以最好的方式利用芳香族氨基酸 (AAA) 的有限可用性，因为哺乳动物不合成它们。烟曲霉中 AAA 分解代谢的关键酶是 AroH，一种吡哆醛 5'-磷酸依赖性芳香氨基转移酶。AroH 最近显示出广泛的底物特异性，除了 AAA 外，还接受 L-犬尿氨酸和 α-氨基己二酸作为氨基供体。鉴于其在真菌对营养条件的适应性中的关键作用，AroH 代表了开发针对烟曲霉相关疾病的创新疗法的潜在目标。我们以 2.4 Å 的分辨率解析了 Af-AroH 的晶体结构，并对酶活性位点的动力学有了新的认识，这似乎对抑制剂的设计至关重要。活性位点口袋的构象可塑性可能与 AroH 的广泛底物特异性有关。