Deazaflavin-dependent nitroreductase
Details
- Name
- Deazaflavin-dependent nitroreductase
- Synonyms
- 1.-.-.-
- F420H(2)-dependent quinone reductase Ddn
- Fqr
- Gene Name
- ddn
- Organism
- Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
- Amino acid sequence
>lcl|BSEQ0051576|Deazaflavin-dependent nitroreductase MPKSPPRFLNSPLSDFFIKWMSRINTWMYRRNDGEGLGGTFQKIPVALLTTTGRKTGQPR VNPLYFLRDGGRVIVAASKGGAEKNPMWYLNLKANPKVQVQIKKEVLDLTARDATDEERA EYWPQLVTMYPSYQDYQSWTDRTIPIVVCEP
- Number of residues
- 151
- Molecular Weight
- 17370.87
- Theoretical pI
- Not Available
- GO Classification
- Functionscoenzyme F420 binding / oxidoreductase activityProcessesoxidation-reduction processComponentscell wall / plasma membrane
- General Function
- Involved in a F420-dependent anti-oxidant mechanism that protects M.tuberculosis against oxidative stress and bactericidal agents. Catalyzes the F420H(2)-dependent two-electron reduction of quinones to dihydroquinones, thereby preventing the formation of cytotoxic semiquinones obtained by the one-electron reduction pathway (PubMed:23240649). In vitro, catalyzes the reduction of both benzoquinone and naphthoquinone analogs; since menaquinone is the sole quinone electron carrier in the respiratory chain in M.tuberculosis, the physiological electron acceptor for Fqr-mediated F420H(2) oxidation is therefore likely to be the endogenous menaquinone found in the membrane fraction of M.tuberculosis (PubMed:23240649). Is able to use F420 species with two and five glutamate residues in its polyglutamate tail (PubMed:22023140). Cannot use NADH or NADPH instead of F420H(2) as the electron donor (PubMed:23240649).
- Specific Function
- Coenzyme f420 binding
- Pfam Domain Function
- F420H2_quin_red (PF04075)
- Transmembrane Regions
- Not Available
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0051577|Deazaflavin-dependent nitroreductase (ddn) ATGCCGAAATCACCGCCGCGGTTTCTGAATTCGCCGCTCAGCGACTTCTTTATCAAGTGG ATGTCACGGATTAATACCTGGATGTACCGCCGCAACGACGGGGAGGGTCTGGGCGGCACC TTCCAGAAGATTCCGGTCGCGCTGCTGACCACCACCGGCCGCAAGACCGGCCAGCCGCGG GTCAACCCGCTCTACTTCCTGCGCGACGGTGGGCGGGTCATTGTCGCGGCCTCCAAGGGC GGCGCGGAGAAGAACCCGATGTGGTACCTCAACCTCAAGGCCAACCCCAAGGTTCAGGTA CAGATCAAAAAGGAAGTGCTGGACCTTACCGCGCGGGACGCGACCGACGAGGAGCGCGCC GAATATTGGCCACAGTTGGTCACGATGTACCCAAGTTATCAGGACTACCAGTCCTGGACC GACCGCACGATCCCGATCGTGGTTTGCGAACCCTGA
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P9WP15 UniProtKB Entry Name DDN_MYCTU - General References
- Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [Article]
- Sinha S, Kosalai K, Arora S, Namane A, Sharma P, Gaikwad AN, Brodin P, Cole ST: Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics. Microbiology. 2005 Jul;151(Pt 7):2411-9. doi: 10.1099/mic.0.27799-0. [Article]
- Manjunatha UH, Boshoff H, Dowd CS, Zhang L, Albert TJ, Norton JE, Daniels L, Dick T, Pang SS, Barry CE 3rd: Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):431-6. doi: 10.1073/pnas.0508392103. Epub 2005 Dec 30. [Article]
- Singh R, Manjunatha U, Boshoff HI, Ha YH, Niyomrattanakit P, Ledwidge R, Dowd CS, Lee IY, Kim P, Zhang L, Kang S, Keller TH, Jiricek J, Barry CE 3rd: PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science. 2008 Nov 28;322(5906):1392-5. doi: 10.1126/science.1164571. [Article]
- Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [Article]
- Gurumurthy M, Mukherjee T, Dowd CS, Singh R, Niyomrattanakit P, Tay JA, Nayyar A, Lee YS, Cherian J, Boshoff HI, Dick T, Barry CE 3rd, Manjunatha UH: Substrate specificity of the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis responsible for the bioreductive activation of bicyclic nitroimidazoles. FEBS J. 2012 Jan;279(1):113-25. doi: 10.1111/j.1742-4658.2011.08404.x. Epub 2011 Nov 14. [Article]
- Gurumurthy M, Rao M, Mukherjee T, Rao SP, Boshoff HI, Dick T, Barry CE 3rd, Manjunatha UH: A novel F(420) -dependent anti-oxidant mechanism protects Mycobacterium tuberculosis against oxidative stress and bactericidal agents. Mol Microbiol. 2013 Feb;87(4):744-55. doi: 10.1111/mmi.12127. Epub 2012 Dec 28. [Article]
- Cellitti SE, Shaffer J, Jones DH, Mukherjee T, Gurumurthy M, Bursulaya B, Boshoff HI, Choi I, Nayyar A, Lee YS, Cherian J, Niyomrattanakit P, Dick T, Manjunatha UH, Barry CE 3rd, Spraggon G, Geierstanger BH: Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824. Structure. 2012 Jan 11;20(1):101-12. doi: 10.1016/j.str.2011.11.001. [Article]