NNR_MYCLE
ID NNR_MYCLE Reviewed; 473 AA.
AC P37391; Q9CCV5;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Bifunctional NAD(P)H-hydrate repair enzyme Nnr;
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 Name=nnr; OrderedLocusNames=ML0373; ORFNames=B229_C2_201, u229g;
OS Mycobacterium leprae (strain TN).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=272631;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Smith D.R., Robison K.;
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=TN;
RX PubMed=11234002; DOI=10.1038/35059006;
RA Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA Barrell B.G.;
RT "Massive gene decay in the leprosy bacillus.";
RL Nature 409:1007-1011(2001).
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA17298.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U00020; AAA17298.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AL583918; CAC29881.1; -; Genomic_DNA.
DR PIR; E86955; E86955.
DR PIR; S72984; S72984.
DR RefSeq; NP_301366.1; NC_002677.1.
DR RefSeq; WP_010907690.1; NC_002677.1.
DR AlphaFoldDB; P37391; -.
DR SMR; P37391; -.
DR STRING; 272631.ML0373; -.
DR EnsemblBacteria; CAC29881; CAC29881; CAC29881.
DR KEGG; mle:ML0373; -.
DR PATRIC; fig|272631.5.peg.630; -.
DR Leproma; ML0373; -.
DR eggNOG; COG0062; Bacteria.
DR eggNOG; COG0063; Bacteria.
DR HOGENOM; CLU_024853_4_0_11; -.
DR OMA; HNGGDAL; -.
DR Proteomes; UP000000806; Chromosome.
DR GO; GO:0052855; F:ADP-dependent NAD(P)H-hydrate dehydratase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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; PS01049; YJEF_C_1; 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..473
FT /note="Bifunctional NAD(P)H-hydrate repair enzyme Nnr"
FT /id="PRO_0000119047"
FT DOMAIN 10..205
FT /note="YjeF N-terminal"
FT DOMAIN 210..473
FT /note="YjeF C-terminal"
FT REGION 1..203
FT /note="NAD(P)H-hydrate epimerase"
FT /evidence="ECO:0000250"
FT REGION 62..66
FT /note="NADPHX 1; for epimerase activity"
FT /evidence="ECO:0000250"
FT REGION 123..129
FT /note="NADPHX 1; for epimerase activity"
FT /evidence="ECO:0000250"
FT REGION 210..473
FT /note="ADP-dependent (S)-NAD(P)H-hydrate dehydratase"
FT /evidence="ECO:0000250"
FT REGION 348..354
FT /note="NADPHX 2; for dehydratase activity"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 152
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 155
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250"
FT BINDING 298
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 382..386
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT BINDING 402..411
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT BINDING 412
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 CONFLICT 66..67
FT /note="DA -> ES (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 47227 MW; 29569CBBD666C81C CRC64;
MRHYYSVAAI RDAEASLLAS LPDGVLMKRA AYGLASVIIR ELAVRTGGVT GRRVCAVVGS
GDNGGDALWA ATFLRRRGAA ADAVLLNPDR VHRKALVAFR KAGGRIVENV SAATDLVIDG
VVGISGSGPL RPAAAAVFAT VSASGVPVVA VDLPSGIDVV TGVINGPAVH AALTVTFGGL
KPVHALADCG DVTLVDIGLD LPDSDILGLQ AADVAAYWPV PGVHDDKYTQ GVTGVLAGSS
TYPGAAVLCT GAAVAATSGM VRYAGSAYTQ VLAHWPEVIA SATPTAAGRV QSWVVGPGLG
IDATATAALW FALETDLPVL VDADGLTMLA AHPDLVINRN APTVLTPHAS EFARLAGTPP
GDDRVGACRK LADSFGATVL LKGNVTVIAD PGGPVYLNPA GQSWAATAGS GDVLSGMIGA
LLAAGLPAAE AAAAAAFVHA RAAALSAADP GPGDVPTSAS RMVSHIRTAL AAL
