NNR_LEIMA
ID NNR_LEIMA Reviewed; 560 AA.
AC Q4QFL5;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Bifunctional NAD(P)H-hydrate repair enzyme;
DE AltName: Full=Nicotinamide nucleotide repair protein;
DE Includes:
DE RecName: Full=ADP-dependent (S)-NAD(P)H-hydrate dehydratase;
DE EC=4.2.1.136;
DE AltName: Full=ADP-dependent NAD(P)HX dehydratase;
DE Includes:
DE RecName: Full=NAD(P)H-hydrate epimerase;
DE EC=5.1.99.6;
DE AltName: Full=NAD(P)HX epimerase;
GN ORFNames=LMJF_14_1190;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/IL/81/Friedlin;
RX PubMed=16020728; DOI=10.1126/science.1112680;
RA Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G.,
RA Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A.,
RA Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M.,
RA Bianchettin G., Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E.,
RA Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M.,
RA De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N.,
RA Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A.,
RA Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S.,
RA Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M.,
RA Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S.,
RA Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M.,
RA Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E.,
RA Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C.,
RA Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K.,
RA Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V.,
RA Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J.,
RA Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D.,
RA Barrell B.G., Myler P.J.;
RT "The genome of the kinetoplastid parasite, Leishmania major.";
RL Science 309:436-442(2005).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the epimerization of the
CC S- and R-forms of NAD(P)HX and the dehydration of the S-form of
CC NAD(P)HX at the expense of ADP, which is converted to AMP. This allows
CC the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that
CC is a result of enzymatic or heat-dependent hydration (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-NADHX + ADP = AMP + H(+) + NADH + phosphate;
CC Xref=Rhea:RHEA:32223, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:64074, ChEBI:CHEBI:456215,
CC ChEBI:CHEBI:456216; EC=4.2.1.136;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-NADPHX + ADP = AMP + H(+) + NADPH + phosphate;
CC Xref=Rhea:RHEA:32235, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:64076, ChEBI:CHEBI:456215,
CC ChEBI:CHEBI:456216; EC=4.2.1.136;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-NADHX = (6S)-NADHX; Xref=Rhea:RHEA:32215,
CC ChEBI:CHEBI:64074, ChEBI:CHEBI:64075; EC=5.1.99.6;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-NADPHX = (6S)-NADPHX; Xref=Rhea:RHEA:32227,
CC ChEBI:CHEBI:64076, ChEBI:CHEBI:64077; EC=5.1.99.6;
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000250};
CC Note=Binds 1 potassium ion per subunit. {ECO:0000250};
CC -!- SIMILARITY: In the N-terminal section; belongs to the NnrE/AIBP family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NnrD/CARKD
CC family. {ECO:0000305}.
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DR EMBL; FR796410; CAJ03189.1; -; Genomic_DNA.
DR RefSeq; XP_001687719.1; XM_001687667.1.
DR AlphaFoldDB; Q4QFL5; -.
DR SMR; Q4QFL5; -.
DR STRING; 5664.LmjF.14.1190; -.
DR EnsemblProtists; CAJ03189; CAJ03189; LMJF_14_1190.
DR GeneID; 5650323; -.
DR KEGG; lma:LMJF_14_1190; -.
DR VEuPathDB; TriTrypDB:LmjF.14.1190; -.
DR VEuPathDB; TriTrypDB:LMJLV39_140019700; -.
DR VEuPathDB; TriTrypDB:LMJSD75_140019200; -.
DR eggNOG; KOG2585; Eukaryota.
DR eggNOG; KOG3974; Eukaryota.
DR HOGENOM; CLU_024853_4_3_1; -.
DR InParanoid; Q4QFL5; -.
DR OMA; HNGGDAL; -.
DR Proteomes; UP000000542; Chromosome 14.
DR GO; GO:0052855; F:ADP-dependent NAD(P)H-hydrate dehydratase activity; ISA:GeneDB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047453; F:ATP-dependent NAD(P)H-hydrate dehydratase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052856; F:NADHX epimerase activity; ISA:GeneDB.
DR GO; GO:0052857; F:NADPHX epimerase activity; ISA:GeneDB.
DR GO; GO:0110051; P:metabolite repair; IBA:GO_Central.
DR GO; GO:0046496; P:nicotinamide nucleotide metabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd01171; YXKO-related; 1.
DR Gene3D; 3.40.1190.20; -; 1.
DR Gene3D; 3.40.50.10260; -; 1.
DR HAMAP; MF_01965; NADHX_dehydratase; 1.
DR HAMAP; MF_01966; NADHX_epimerase; 1.
DR InterPro; IPR017953; Carbohydrate_kinase_pred_CS.
DR InterPro; IPR000631; CARKD.
DR InterPro; IPR030677; Nnr.
DR InterPro; IPR029056; Ribokinase-like.
DR InterPro; IPR004443; YjeF_N_dom.
DR InterPro; IPR036652; YjeF_N_dom_sf.
DR Pfam; PF01256; Carb_kinase; 1.
DR Pfam; PF03853; YjeF_N; 1.
DR PIRSF; PIRSF017184; Nnr; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
DR SUPFAM; SSF64153; SSF64153; 1.
DR TIGRFAMs; TIGR00196; yjeF_cterm; 1.
DR TIGRFAMs; TIGR00197; yjeF_nterm; 1.
DR PROSITE; PS01050; YJEF_C_2; 1.
DR PROSITE; PS51383; YJEF_C_3; 1.
DR PROSITE; PS51385; YJEF_N; 1.
PE 3: Inferred from homology;
KW ATP-binding; Isomerase; Lyase; Metal-binding; Multifunctional enzyme; NAD;
KW NADP; Nucleotide-binding; Potassium; Reference proteome.
FT CHAIN 1..560
FT /note="Bifunctional NAD(P)H-hydrate repair enzyme"
FT /id="PRO_0000416435"
FT DOMAIN 29..235
FT /note="YjeF N-terminal"
FT DOMAIN 249..547
FT /note="YjeF C-terminal"
FT REGION 1..241
FT /note="NAD(P)H-hydrate epimerase"
FT /evidence="ECO:0000250"
FT REGION 77..81
FT /note="NADPHX 1; for epimerase activity"
FT /evidence="ECO:0000250"
FT REGION 149..155
FT /note="NADPHX 1; for epimerase activity"
FT /evidence="ECO:0000250"
FT REGION 249..560
FT /note="ADP-dependent (S)-NAD(P)H-hydrate dehydratase"
FT /evidence="ECO:0000250"
FT REGION 417..423
FT /note="NADPHX 2; for dehydratase activity"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 145
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 160
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="1"
FT /ligand_note="for epimerase activity"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="1"
FT /ligand_note="for epimerase activity"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 351
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="2"
FT /ligand_note="for dehydratase activity"
FT /evidence="ECO:0000250"
FT BINDING 454..458
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT BINDING 475..484
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT BINDING 485
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="2"
FT /ligand_note="for dehydratase activity"
FT /evidence="ECO:0000250"
SQ SEQUENCE 560 AA; 58434 MW; 1697B100AD3BB3F9 CRC64;
MLSRLSERCT IATGLEQVLR HYVWSAAWLR DAEPAAAASE NIDLSGLMER AGRAAYDVFA
NLYTSQKHWL ILVGSGNNGG DGYVIARHAR EAGKIVTVLR MPHSKPLPTE AASAQHAWKA
VGGTESTMSP GAPLQLPADV DLIVDGLLGT GICGPPREQY ADVIRHINGL PVPRVAIDIP
SGLNAETGEA AGACVKADHT ATFICLKPGL LTGQAKDYVG QLHYRSLGLE DWMTAPERMR
VALCRRVALD DVYEYFGIRR SALAHKGSCG KAILVGGDHG FGGAALMSAE ACVTVGAGLT
RVLTRPEYAA PLLTRCPEAM VTAVETDTGE QLKQQMLEAF EWASTLAVGP GLGTGAYGQA
ALTAALRHAE LHQDKTLVLD ADALNLLAGC LHGREGGAAA GARKHLPVLP NSIITPHPGE
AARLLDCRVA DVEKDRLAAA RRLAAILGGT CLLKGPGTIV HCHSSAKTAI VDAGNAGMAS
GGMGDVLTGL LAGLAAQRMH DTFDTTCAGA LVHGVAADMV AAEDGRGTRG IRATELIHRV
PLIVNASGPS PASRQRPSGQ
