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5xur

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Crystal Structure of Rv2466c C22S Mutant

Structural highlights

5xur is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.996Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRLR_MYCTU In vitro, the reduced form of Rv2466c catalyzes the reduction and activation of TP053, which is a thienopyrimidine derivative drug that can kill both replicating and non-replicating M.tuberculosis.^[1]

Publication Abstract from PubMed

The success of Mycobacterium tuberculosis (Mtb) as a pathogen depends on the redundant and complex mechanisms it has evolved for resisting nitrosative and oxidative stresses inflicted by host immunity. Improving our understanding of these defense pathways can reveal vulnerable points in Mtb pathogenesis. In this study, we combined genetic, structural, computational, biochemical, and biophysical approaches to identify a novel enzyme class represented by Rv2466c. We show that Rv2466c is a mycothiol-dependent nitroreductase of Mtb and can reduce the nitro group of a novel mycobactericidal compound using mycothiol as a cofactor. In addition to its function as a nitroreductase, Rv2466c confers partial protection to menadione stress.

Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.,Negri A, Javidnia P, Mu R, Zhang X, Vendome J, Gold B, Roberts J, Barman D, Ioerger T, Sacchettini JC, Jiang X, Burns-Huang K, Warrier T, Ling Y, Warren JD, Oren DA, Beuming T, Wang H, Wu J, Li H, Rhee KY, Nathan CF, Liu G, Somersan-Karakaya S ACS Infect Dis. 2018 Feb 21. doi: 10.1021/acsinfecdis.7b00111. PMID:29465985^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Albesa-Jove D, Chiarelli LR, Makarov V, Pasca MR, Urresti S, Mori G, Salina E, Vocat A, Comino N, Mohorko E, Ryabova S, Pfieiffer B, Lopes Ribeiro AL, Rodrigo-Unzueta A, Tersa M, Zanoni G, Buroni S, Altmann KH, Hartkoorn RC, Glockshuber R, Cole ST, Riccardi G, Guerin ME. Rv2466c mediates the activation of TP053 to kill replicating and non-replicating Mycobacterium tuberculosis. ACS Chem Biol. 2014 Jul 18;9(7):1567-75. doi: 10.1021/cb500149m. Epub 2014 Jun, 13. PMID:24877756 doi:http://dx.doi.org/10.1021/cb500149m
↑ Negri A, Javidnia P, Mu R, Zhang X, Vendome J, Gold B, Roberts J, Barman D, Ioerger T, Sacchettini JC, Jiang X, Burns-Huang K, Warrier T, Ling Y, Warren JD, Oren DA, Beuming T, Wang H, Wu J, Li H, Rhee KY, Nathan CF, Liu G, Somersan-Karakaya S. Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis. ACS Infect Dis. 2018 Feb 21. doi: 10.1021/acsinfecdis.7b00111. PMID:29465985 doi:http://dx.doi.org/10.1021/acsinfecdis.7b00111