NNR_LEIIN
ID NNR_LEIIN Reviewed; 560 AA.
AC A4HW65;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 73.
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=LINJ_14_1270;
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).
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; FR796446; CAM66687.1; -; Genomic_DNA.
DR RefSeq; XP_001464306.1; XM_001464269.1.
DR AlphaFoldDB; A4HW65; -.
DR SMR; A4HW65; -.
DR STRING; 5671.XP_001464306.1; -.
DR GeneID; 5067633; -.
DR KEGG; lif:LINJ_14_1270; -.
DR VEuPathDB; TriTrypDB:LINF_140018300; -.
DR eggNOG; KOG2585; Eukaryota.
DR eggNOG; KOG3974; Eukaryota.
DR InParanoid; A4HW65; -.
DR OMA; HNGGDAL; -.
DR Proteomes; UP000008153; Chromosome 14.
DR GO; GO:0052855; F:ADP-dependent NAD(P)H-hydrate dehydratase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0052857; F:NADPHX epimerase activity; IEA:UniProtKB-EC.
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_0000416434"
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; 58328 MW; A2E3B927D9135322 CRC64;
MLSRLSERCS IATGLEQVLR RHVWSAAWLR DAEPAAAASQ NIDLSCLMER AGRAAYDVFS
NLYTSQQHWL ILVGSGNNGG DGYVIARHAR EAGKIVTVLC MPHSKPLPAE AASAQHAWKA
VGGTETTMNP GAPLQLPADV DLIVDGLLGT GICGPPREQY EDVIRHINGL PVPRVAIDIP
SGLNAETGEV AGACVKADHT ATFICLKPGL LTGQAKDYVG QLHYRSLGLE DWMTAPERMR
AALCRRVALD DVYEYFGIRR SALAHKGRCG KVILVGGDHG FGGATLMSAE ACVTVGAGLT
RVLTRPEYAA PLLTRCPEAM VTAVETDTGG QLEQQMLAAF EWASTLAVGP GLGTGAYGQA
ALTAALRHAE VHQDKTLVLD ADALNLLAGR LHGKEGGAAA GAGKHLPVLP NSIITPHPGE
AARLLACRVA DVEKDRLAAA RRLAAILGGT CLLKGPGTIV HCHSSAKTAI VDAGNAGMAS
GGMGDVLTGL LAGLAAQRMH DTFNTTCAGA LVHGVAADMV AAEDGRGTRG IRATELIHRV
PLIVNASGPS PATRQRSSGP
