5JAB

Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis.

(2016) Protein Sci 25: 1692-1709

• PubMed: 27364382 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1002/pro.2975
• Primary Citation of Related Structures:  
  5JAB


• PubMed 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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Organizational Affiliation: 

Research School of Chemistry, The Australian National University, Canberra, ACT, 2601, Australia.