5JAB

Structure of the biliverdin reductase Rv2074 from Mycobacterium tuberculosis in complex with F420

Summary for 5JAB

• Entry DOI: 10.2210/pdb5jab/pdb
• Descriptor: Biliverdin reductase Rv2074, COENZYME F420-3, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: biliverdin reductase, split beta-barrel fold, flavin/deazaflavin oxidoreductase, f420 binding protein, oxidoreductase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Cellular location: Cell surface : P9WLL7
• Total number of polymer chains: 4
• Total formula weight: 63019.76

Authors

Ahmed, F.H.,Carr, P.D.,Jackson, C.J. (deposition date: 2016-04-12, release date: 2016-07-13, Last modification date: 2023-09-27)

Primary citation

Ahmed, F.H.,Mohamed, A.E.,Carr, P.D.,Lee, B.M.,Condic-Jurkic, K.,O'Mara, M.L.,Jackson, C.J.
Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis.
Protein Sci., 25:1692-1709, 2016

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.

PubMed: 27364382
DOI: 10.1002/pro.2975

Experimental method

X-RAY DIFFRACTION (1.65 Å)