AI Article Synopsis
- Bilirubin, an antioxidant, is formed from biliverdin through a reaction catalyzed by specific enzymes called biliverdin reductases (BVRs).
- Rv2074, an F420 H2-dependent BVR found in Mycobacterium tuberculosis, is structurally different from previously studied BVRs and plays a role in this process.
- The researchers characterized Rv2074 using various methods, uncovering its crystal structure and catalytic mechanism, which may enhance M. tuberculosis's ability to evade the immune system through bilirubin's antioxidant properties.
Article Abstract
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 F420 H2 -dependent BVRs (F-BVRs) that are exclusively found in Actinobacteria. We have solved the crystal structure of Rv2074 bound to its cofactor, F420 , 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338246 | PMC |
| http://dx.doi.org/10.1002/pro.2975 | DOI Listing |
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