Structural highlights
FunctionFBVR_MYCTU Catalyzes the F420H(2)-dependent reduction of biliverdin-IXalpha at C10 position, leading to bilirubin-IXalpha, a potent antioxidant. As biliverdin-IXalpha is produced in high amounts in macrophages infected with M.tuberculosis, its reduction by Rv2074 may play a role in protecting mycobacteria against oxidative stress, aiding the persistence of M.tuberculosis infection.[1] Publication Abstract from PubMedBilirubin 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 Rossman-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. This article is protected by copyright. All rights reserved. Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis.,Ahmed FH, Mohamed AE, Carr PD, Lee BM, Condic-Jurkic K, O'Mara ML, Jackson CJ Protein Sci. 2016 Jul 1. doi: 10.1002/pro.2975. PMID:27364382[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 10:56, 6 September 2023.