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
Functions
coenzyme F420 binding / oxidoreductase activity
Processes
oxidation-reduction process
Components
cell 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
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
ResourceLink
UniProtKB IDP9WP15
UniProtKB Entry NameDDN_MYCTU
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11637Delamanidapproved, investigationalnosubstrateDetails
DB05154PretomanidapprovedunknownsubstrateDetails