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Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.

BackgroundLung adenocarcinoma, the main subtype of non-small cell lung cancer, leading one of the most aggressive and fatal causes of malignant deaths around the world. Scavenger receptor class A member 5 (SCARA5), a newly discovered tumor suppressor gene, belonged to the SR family. The present study’s object was to explore the clinical impacts of SCARA5 in lung adenocarcinoma treatment. MethodsSCARA5 expressions in 120 paired lung adenocarcinoma patients’ tissues and cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). CCK-8, EdU, flow cytometry, and western blot assays further demonstrated the significance of SCARA5 on A549 cell growth. Then, the relationships between the expression level of SCARA5 and pathological factors were analyzed. Finally, the receiver operating characteristic (ROC) curve and overall survival analysis was carried out to verify the diagnostic and prognostic significance of SCARA5 in lung adenocarcinoma. ResultsSCARA5 was prominently decreased in lung adenocarcinoma cells and tissues compared with human bronchial epithelial cells and para-carcinoma non-tumor tissues. Meanwhile, SCARA5 expression was strongly correlated with smoking (P = 0.0011), TNM stage (P < 0.0001) and lymph node metastasis (P = 0.0005). Furthermore, SCARA5 may be a crucial biomarker for lung adenocarcinoma diagnosis with an area under the curve (AUC) of 0.9102 while SCARA5 could significantly reduce overall survival (OS; P = 0.0006). In vitro experiments, we found that SCARA5 overexpressing could significantly hinder A549 cell proliferation but facilitate apoptosis through the AKT signaling pathway. ConclusionsSCARA5 might be an important diagnostic and prognostic biomarker for patients with lung adenocarcinoma.

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