Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
Biochem J. 2012 Sep 1;446(2):253-60. doi: 10.1042/BJ20120416.
KFase (kynurenine formamidase), also known as arylformamidase and formylkynurenine formamidase, efficiently catalyses the hydrolysis of NFK (N-formyl-L-kynurenine) to kynurenine. KFase is the second enzyme in the kynurenine pathway of tryptophan metabolism. A number of intermediates formed in the kynurenine pathway are biologically active and implicated in an assortment of medical conditions, including cancer, schizophrenia and neurodegenerative diseases. Consequently, enzymes involved in the kynurenine pathway have been considered potential regulatory targets. In the present study, we report, for the first time, the biochemical characterization and crystal structures of Drosophila melanogaster KFase conjugated with an inhibitor, PMSF. The protein architecture of KFase reveals that it belongs to the α/β hydrolase fold family. The PMSF-binding information of the solved conjugated crystal structure was used to obtain a KFase and NFK complex using molecular docking. The complex is useful for understanding the catalytic mechanism of KFase. The present study provides a molecular basis for future efforts in maintaining or regulating kynurenine metabolism through the molecular and biochemical regulation of KFase.
KFase（犬尿氨酸 formamidase），也称为芳基 formamidase 和甲酰基犬尿氨酸 formamidase，能有效地催化 NFK（N-甲酰基-L-犬尿氨酸）水解为犬尿氨酸。KFase 是色氨酸代谢中犬尿氨酸途径的第二种酶。犬尿氨酸途径中形成的许多中间产物具有生物活性，并与多种医学病症有关，包括癌症、精神分裂症和神经退行性疾病。因此，参与犬尿氨酸途径的酶已被认为是潜在的调节靶点。在本研究中，我们首次报道了与抑制剂 PMSF 缀合的果蝇 KFase 的生化特征和晶体结构。KFase 的蛋白质结构表明它属于 α/β 水解酶折叠家族。所解决的缀合晶体结构的 PMSF 结合信息用于使用分子对接获得 KFase 和 NFK 复合物。该复合物有助于理解 KFase 的催化机制。本研究为通过 KFase 的分子和生化调节来维持或调节犬尿氨酸代谢的未来努力提供了分子基础。
