NNR_LEIBR
ID NNR_LEIBR Reviewed; 561 AA.
AC A4H7T9;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 71.
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=LBRM_14_1360;
OS Leishmania braziliensis.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania;
OC Leishmania braziliensis species complex.
OX NCBI_TaxID=5660;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/BR/75/M2904;
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; FR798988; CAM37606.1; -; Genomic_DNA.
DR RefSeq; XP_001563422.1; XM_001563372.1.
DR AlphaFoldDB; A4H7T9; -.
DR SMR; A4H7T9; -.
DR STRING; 5660.A4H7T9; -.
DR GeneID; 5413933; -.
DR KEGG; lbz:LBRM_14_1360; -.
DR VEuPathDB; TriTrypDB:LbrM.14.1360; -.
DR VEuPathDB; TriTrypDB:LBRM2903_140018300; -.
DR InParanoid; A4H7T9; -.
DR OMA; HNGGDAL; -.
DR Proteomes; UP000007258; 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..561
FT /note="Bifunctional NAD(P)H-hydrate repair enzyme"
FT /id="PRO_0000416433"
FT DOMAIN 29..235
FT /note="YjeF N-terminal"
FT DOMAIN 249..548
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..561
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 561 AA; 58658 MW; A6FB974C180B1B0D CRC64;
MLSRISERCT AVTGLEQVLC RHVWSAAWLR DAEPAAAASQ SIDLSCLMER AGLAAYDVFA
SLYASQRHWL ILVGSGNNGG DGYVIARHAR EAGRKVTVLS MPHSKPLPTE ATNAQHAWQA
VGGTETMINP GTSLHLPTDV DLVVDGLLGT GISGPPREHY EEVIRHINAL PVPRVAIDIP
SGLNAETGEA AGACVKADHT ATFICLKPGL LTGQARDYVG QLHYRSLGLE EWMIAAERMD
AALCRRVALG DVYGYFSTRR SAVAHKGSCG KVVLIGGDHG FGGAILMSAE ACLTIGAGLT
RVLTRPEYVA PLLTRCPEVM VTAVETETSG QLEQQMVEAF EWASTLAVGP GLGTGAYGQA
ALSAALQQAE MHQDKTLVLD ADALNLLAER LHSKEMGAAV GAGKYLPVLP NSIITPHPGE
AARLLACRVA DVEKDRLAAA RRLAAILGGT CLLKGPGTVV HCQSSGKTAI VDAGNAGMAS
GGMGDVLTGL LAGLAAQRMM HDTFDTTCAA ALVHGVAADM VAAEDGRGTR GIRATELIPR
IPFIVNASVP SSATQQRPSG L
