NTR2_LEIIN
ID NTR2_LEIIN Reviewed; 365 AA.
AC E9AGH7;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Probable flavin mononucleotide-dependent alkene reductase {ECO:0000305|PubMed:27812217};
DE EC=1.3.1.- {ECO:0000305|PubMed:27812217};
DE AltName: Full=Flavin mononucleotide-dependent nitroreductase {ECO:0000303|PubMed:27812217};
DE EC=1.7.1.- {ECO:0000269|PubMed:27812217};
DE AltName: Full=NTR2 {ECO:0000303|PubMed:27812217};
GN ORFNames=LINJ.12.0730 {ECO:0000312|EMBL:CBZ08477.1};
OS Leishmania infantum.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5671;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JPCM5;
RX PubMed=17572675; DOI=10.1038/ng2053;
RA Peacock C.S., Seeger K., Harris D., Murphy L., Ruiz J.C., Quail M.A.,
RA Peters N., Adlem E., Tivey A., Aslett M., Kerhornou A., Ivens A.,
RA Fraser A., Rajandream M.-A., Carver T., Norbertczak H., Chillingworth T.,
RA Hance Z., Jagels K., Moule S., Ormond D., Rutter S., Sqaures R.,
RA Whitehead S., Rabbinowitsch E., Arrowsmith C., White B., Thurston S.,
RA Bringaud F., Baldauf S.L., Faulconbridge A., Jeffares D., Depledge D.P.,
RA Oyola S.O., Hilley J.D., Brito L.O., Tosi L.R.O., Barrell B., Cruz A.K.,
RA Mottram J.C., Smith D.F., Berriman M.;
RT "Comparative genomic analysis of three Leishmania species that cause
RT diverse human disease.";
RL Nat. Genet. 39:839-847(2007).
RN [2]
RP FUNCTION AS A NITROREDUCTASE, COFACTOR, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, DISRUPTION PHENOTYPE, SUBUNIT, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=27812217; DOI=10.1371/journal.ppat.1005971;
RA Wyllie S., Roberts A.J., Norval S., Patterson S., Foth B.J., Berriman M.,
RA Read K.D., Fairlamb A.H.;
RT "Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in
RT Leishmania.";
RL PLoS Pathog. 12:E1005971-E1005971(2016).
CC -!- FUNCTION: May function as a flavin mononucleotide (FMN)-dependent
CC alkene reductase on substrates carrying alpha,beta-unsaturated carbonyl
CC groups (ketones, aldehydes, carboxylic acids, esters, lactones or
CC cyclic imides). The catalysis depends on NAD(P)H, which acts as hydride
CC donor for the reduction. Seems to be involved in metabolic pathways
CC required for efficient replication of amastigotes within macrophages.
CC {ECO:0000305|PubMed:27812217}.
CC -!- FUNCTION: Acts as a FMN-dependent nitroreductase that activates anti-
CC leishmanial bicyclic nitroaromatic prodrugs including delamanid, DNDI-
CC VL-2098 and (R)-PA-824, forming toxic products that kill the parasites.
CC {ECO:0000269|PubMed:27812217}.
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:27812217};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:27812217}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:27812217}.
CC -!- DEVELOPMENTAL STAGE: Detected in all developmental stages: log phase
CC promastigotes, metacyclic promastigotes and axenic amastigotes.
CC {ECO:0000269|PubMed:27812217}.
CC -!- DISRUPTION PHENOTYPE: Knockout parasites show reduced replication
CC within macrophages, but are resistant to bicyclic nitro-drugs including
CC delamanid and DNDI-VL-2098. Sensitivity to bicyclic nitro-drugs is
CC fully restored on expression of this reductase.
CC {ECO:0000269|PubMed:27812217}.
CC -!- SIMILARITY: Belongs to the NADH:flavin oxidoreductase/NADH oxidase
CC family. {ECO:0000305}.
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DR EMBL; FR796444; CBZ08477.1; -; Genomic_DNA.
DR RefSeq; XP_003392329.1; XM_003392281.1.
DR AlphaFoldDB; E9AGH7; -.
DR SMR; E9AGH7; -.
DR STRING; 5671.XP_003392329.1; -.
DR GeneID; 10966078; -.
DR KEGG; lif:LINJ.12.0730; -.
DR VEuPathDB; TriTrypDB:LINF_120015500; -.
DR eggNOG; KOG0134; Eukaryota.
DR InParanoid; E9AGH7; -.
DR OMA; MQIMHGG; -.
DR Proteomes; UP000008153; Chromosome 12.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016657; F:oxidoreductase activity, acting on NAD(P)H, nitrogenous group as acceptor; IDA:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001155; OxRdtase_FMN_N.
DR InterPro; IPR045247; Oye-like.
DR PANTHER; PTHR22893; PTHR22893; 1.
DR Pfam; PF00724; Oxidored_FMN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Flavoprotein; FMN; NAD; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..365
FT /note="Probable flavin mononucleotide-dependent alkene
FT reductase"
FT /id="PRO_0000444985"
FT ACT_SITE 191
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P42593"
FT BINDING 30..32
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
FT BINDING 63
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
FT BINDING 105
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
FT BINDING 238
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
FT BINDING 303
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
FT BINDING 324..325
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9FUP0"
SQ SEQUENCE 365 AA; 39451 MW; 7D8F04F4159A6BC2 CRC64;
MSAASKSIDV MLKPLLVGGR PISNRFVMAP LTRCRADDNH VPTAAMVKHY SDRASMGLII
TEATQIQKGY STFAHEGGIY DKEHVDGWRK VTDAVHDKGG IIFCQIHNGG RSTVPSNVDE
GVRIVAPSAV AITGHKCAGS FARNGKTQPY PVPHAMAAEE IASYVNLYAA AARNAIAAGF
DGVEVHGANG YLIDQFLKTS SNQRTDEYGG SIENRCRFLF EVLDAVIQAI GRERVGLRIS
PLNSFNDQSD EDPQALTRYI CSQLNLRTIA FLDVMRGDFF SPARGADKWA REEYEGVLFT
GMSFEIEEAA KAVESGAADA VVFGTKALAN PDLVARAVAG APLNKPDPAT FYTTGEAGYN
DYPFM
