Rv2074 is a Novel F420 H2 -dependent Biliverdin Reductase in Mycobacterium Tuberculosis

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2016 Jul 2

PMID 27364382

Citations 15

Authors

F Hafna Ahmed

A Elaaf Mohamed

Paul D Carr

Brendon M Lee

Karmen condic-Jurkic

Megan L OMara

Colin J Jackson

Affiliations

Soon will be listed here.

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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