DDN_MYCTO
ID DDN_MYCTO Reviewed; 151 AA.
AC P9WP14; L0TD35; P71854; Q7D5B2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Deazaflavin-dependent nitroreductase {ECO:0000250|UniProtKB:P9WP15};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:P9WP15};
DE AltName: Full=F420H(2)-dependent quinone reductase Ddn {ECO:0000250|UniProtKB:P9WP15};
DE Short=Fqr {ECO:0000250|UniProtKB:P9WP15};
DE EC=1.1.98.- {ECO:0000250|UniProtKB:P9WP15};
GN Name=ddn; OrderedLocusNames=MT3651;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Involved in a F420-dependent anti-oxidant mechanism that
CC protects M.tuberculosis against oxidative stress and bactericidal
CC agents. Catalyzes the F420H(2)-dependent two-electron reduction of
CC quinones to dihydroquinones, thereby preventing the formation of
CC cytotoxic semiquinones obtained by the one-electron reduction pathway.
CC In vitro, catalyzes the reduction of both benzoquinone and
CC naphthoquinone analogs; since menaquinone is the sole quinone electron
CC carrier in the respiratory chain in M.tuberculosis, the physiological
CC electron acceptor for Fqr-mediated F420H(2) oxidation is therefore
CC likely to be the endogenous menaquinone found in the membrane fraction
CC of M.tuberculosis. Is able to use F420 species with two and five
CC glutamate residues in its polyglutamate tail. Cannot use NADH or NADPH
CC instead of F420H(2) as the electron donor.
CC {ECO:0000250|UniProtKB:P9WP15}.
CC -!- FUNCTION: Is involved in the bioreductive activation of bicyclic 4-
CC nitroimidazole prodrugs such as PA-824 and delamanid developed for
CC anti-tuberculosis therapy against both replicating and persistent
CC bacteria. It converts PA-824 into three primary metabolites resulting
CC from reduction of the imidazole ring at C-3; the major one is the
CC corresponding des-nitroimidazole that generates lethal reactive
CC nitrogen species, including nitric oxide (NO), which appears to be
CC responsible for the anaerobic killing activity. Ddn uses the reduced
CC F420 produced by FGD1 to activate PA-824. Delamanid (OPC-67683) is also
CC reduced by Ddn to its des-nitro form. {ECO:0000250|UniProtKB:P9WP15}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinol + H(+) + oxidized coenzyme F420-(gamma-L-Glu)(n) = a
CC quinone + reduced coenzyme F420-(gamma-L-Glu)(n);
CC Xref=Rhea:RHEA:39663, Rhea:RHEA-COMP:12939, Rhea:RHEA-COMP:14378,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:24646, ChEBI:CHEBI:132124,
CC ChEBI:CHEBI:133980, ChEBI:CHEBI:139511;
CC Evidence={ECO:0000250|UniProtKB:P9WP15};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P9WP15};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P9WP15}.
CC -!- SIMILARITY: Belongs to the F420H(2)-dependent quinone reductase family.
CC {ECO:0000305}.
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DR EMBL; AE000516; AAK48010.1; -; Genomic_DNA.
DR PIR; D70677; D70677.
DR RefSeq; WP_003419309.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WP14; -.
DR SMR; P9WP14; -.
DR EnsemblBacteria; AAK48010; AAK48010; MT3651.
DR GeneID; 45427531; -.
DR KEGG; mtc:MT3651; -.
DR PATRIC; fig|83331.31.peg.3932; -.
DR HOGENOM; CLU_114921_1_1_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 2.30.110.10; -; 1.
DR InterPro; IPR004378; F420H2_quin_Rdtase.
DR InterPro; IPR012349; Split_barrel_FMN-bd.
DR Pfam; PF04075; F420H2_quin_red; 1.
DR TIGRFAMs; TIGR00026; hi_GC_TIGR00026; 1.
PE 3: Inferred from homology;
KW Cell membrane; Membrane; Oxidoreductase.
FT CHAIN 1..151
FT /note="Deazaflavin-dependent nitroreductase"
FT /id="PRO_0000427031"
FT BINDING 54..56
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WP15"
FT BINDING 60..65
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WP15"
FT BINDING 76..79
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WP15"
FT BINDING 87..91
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WP15"
FT BINDING 133
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WP15"
SQ SEQUENCE 151 AA; 17371 MW; 41534E55D948FB52 CRC64;
MPKSPPRFLN SPLSDFFIKW MSRINTWMYR RNDGEGLGGT FQKIPVALLT TTGRKTGQPR
VNPLYFLRDG GRVIVAASKG GAEKNPMWYL NLKANPKVQV QIKKEVLDLT ARDATDEERA
EYWPQLVTMY PSYQDYQSWT DRTIPIVVCE P
