Rv2074 is a novel F420H2-dependent biliverdin reductase in Mycobacterium tuberculosis

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• 作者：F. Hafna Ahmed ; A. Elaaf Mohamed ; Paul D. Carr ; Brendon M. Lee ; Karmen Condic-Jurkic ; Megan L. O' ; Mara and Colin J. Jackson
• 刊名：Protein Science
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：25
• 期：9
• 页码：1692-1709
• 全文大小：4204K
• ISSN：1469-896X

文摘

Bilirubin is a potent antioxidant that is produced from the reduction of the heme degradation product biliverdin. In mammalian cells and Cyanobacteria, NADH/NADPH-dependent biliverdin reductases (BVRs) of the Rossmann-fold have been shown to catalyze this reaction. Here, we describe the characterization of Rv2074 from Mycobacterium tuberculosis, which belongs to a structurally and mechanistically distinct family of Fb>420b>Hb>2b>-dependent BVRs (F-BVRs) that are exclusively found in Actinobacteria. We have solved the crystal structure of Rv2074 bound to its cofactor, Fb>420b>, and used this alongside molecular dynamics simulations, site-directed mutagenesis and NMR spectroscopy to elucidate its catalytic mechanism. The production of bilirubin by Rv2074 could exploit the anti-oxidative properties of bilirubin and contribute to the range of immuno-evasive mechanisms that have evolved in M. tuberculosis to allow persistent infection.