NNR_THEMA
ID NNR_THEMA Reviewed; 490 AA.
AC Q9X024;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 109.
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=TM_0922;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS).
RG Joint Center for Structural Genomics (JCSG);
RT "Crystal structure of hypothetical protein (TM0922) from Thermotoga
RT maritima at 2.27 A resolution.";
RL Submitted (SEP-2005) to the PDB data bank.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEXES WITH POTASSIUM; ADP AND
RP NAD(P)HX ANALOGS.
RX PubMed=22940582; DOI=10.1016/j.str.2012.07.016;
RA Shumilin I.A., Cymborowski M., Chertihin O., Jha K.N., Herr J.C.,
RA Lesley S.A., Joachimiak A., Minor W.;
RT "Identification of unknown protein function using metabolite cocktail
RT screening.";
RL Structure 20:1715-1725(2012).
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; AE000512; AAD36003.1; -; Genomic_DNA.
DR PIR; C72317; C72317.
DR RefSeq; NP_228730.1; NC_000853.1.
DR RefSeq; WP_010865220.1; NC_023151.1.
DR PDB; 2AX3; X-ray; 2.27 A; A=1-490.
DR PDB; 3RRB; X-ray; 2.40 A; A=1-490.
DR PDB; 3RRE; X-ray; 2.15 A; A=1-490.
DR PDB; 3RRF; X-ray; 2.10 A; A=1-490.
DR PDB; 3RRJ; X-ray; 2.50 A; A=1-490.
DR PDB; 3RS8; X-ray; 2.10 A; A=1-490.
DR PDB; 3RS9; X-ray; 2.10 A; A=1-490.
DR PDB; 3RSF; X-ray; 2.30 A; A=1-490.
DR PDB; 3RSG; X-ray; 2.10 A; A=1-490.
DR PDB; 3RSQ; X-ray; 2.05 A; A=1-490.
DR PDB; 3RSS; X-ray; 1.95 A; A=1-490.
DR PDB; 3RT7; X-ray; 2.10 A; A=1-490.
DR PDB; 3RT9; X-ray; 1.95 A; A=1-490.
DR PDB; 3RTA; X-ray; 1.95 A; A=1-490.
DR PDB; 3RTB; X-ray; 2.10 A; A=1-490.
DR PDB; 3RTC; X-ray; 2.10 A; A=1-490.
DR PDB; 3RTD; X-ray; 2.30 A; A=1-490.
DR PDB; 3RTE; X-ray; 2.10 A; A=1-490.
DR PDB; 3RTG; X-ray; 2.05 A; A=1-490.
DR PDB; 3RU2; X-ray; 2.20 A; A=1-490.
DR PDB; 3RU3; X-ray; 2.60 A; A=1-490.
DR PDBsum; 2AX3; -.
DR PDBsum; 3RRB; -.
DR PDBsum; 3RRE; -.
DR PDBsum; 3RRF; -.
DR PDBsum; 3RRJ; -.
DR PDBsum; 3RS8; -.
DR PDBsum; 3RS9; -.
DR PDBsum; 3RSF; -.
DR PDBsum; 3RSG; -.
DR PDBsum; 3RSQ; -.
DR PDBsum; 3RSS; -.
DR PDBsum; 3RT7; -.
DR PDBsum; 3RT9; -.
DR PDBsum; 3RTA; -.
DR PDBsum; 3RTB; -.
DR PDBsum; 3RTC; -.
DR PDBsum; 3RTD; -.
DR PDBsum; 3RTE; -.
DR PDBsum; 3RTG; -.
DR PDBsum; 3RU2; -.
DR PDBsum; 3RU3; -.
DR AlphaFoldDB; Q9X024; -.
DR SMR; Q9X024; -.
DR DIP; DIP-59950N; -.
DR STRING; 243274.THEMA_00025; -.
DR DNASU; 898596; -.
DR EnsemblBacteria; AAD36003; AAD36003; TM_0922.
DR KEGG; tma:TM0922; -.
DR PATRIC; fig|243274.5.peg.936; -.
DR eggNOG; COG0062; Bacteria.
DR eggNOG; COG0063; Bacteria.
DR InParanoid; Q9X024; -.
DR OMA; HNGGDAL; -.
DR BRENDA; 4.2.1.136; 6331.
DR EvolutionaryTrace; Q9X024; -.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0052855; F:ADP-dependent NAD(P)H-hydrate dehydratase activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0052857; F:NADPHX epimerase activity; IBA:GO_Central.
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; 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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Isomerase; Lyase; Metal-binding;
KW Multifunctional enzyme; NAD; NADP; Nucleotide-binding; Potassium;
KW Reference proteome.
FT CHAIN 1..490
FT /note="Bifunctional NAD(P)H-hydrate repair enzyme Nnr"
FT /id="PRO_0000416413"
FT DOMAIN 1..204
FT /note="YjeF N-terminal"
FT DOMAIN 212..488
FT /note="YjeF C-terminal"
FT REGION 1..204
FT /note="NAD(P)H-hydrate epimerase"
FT /evidence="ECO:0000250"
FT REGION 51..55
FT /note="NADPHX 1; for epimerase activity"
FT REGION 118..124
FT /note="NADPHX 1; for epimerase activity"
FT REGION 212..490
FT /note="ADP-dependent (S)-NAD(P)H-hydrate dehydratase"
FT /evidence="ECO:0000250"
FT REGION 366..372
FT /note="NADPHX 2; for dehydratase activity"
FT BINDING 52
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT BINDING 114
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT BINDING 129
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="1"
FT /ligand_note="for epimerase activity"
FT BINDING 147
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="1"
FT /ligand_note="for epimerase activity"
FT BINDING 150
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT BINDING 317
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="2"
FT /ligand_note="for dehydratase activity"
FT BINDING 402..406
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT BINDING 421..430
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT BINDING 431
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /ligand_label="2"
FT /ligand_note="for dehydratase activity"
FT HELIX 2..10
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 16..35
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:3RTB"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 51..63
FT /evidence="ECO:0007829|PDB:3RTA"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 103..108
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 127..138
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:3RTA"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 167..174
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 247..257
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 261..268
FT /evidence="ECO:0007829|PDB:3RTA"
FT TURN 269..272
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 299..306
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 322..334
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 343..347
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 351..356
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 367..374
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 385..395
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 397..401
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 403..409
FT /evidence="ECO:0007829|PDB:3RTA"
FT STRAND 414..417
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 429..442
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 447..463
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:3RTA"
FT HELIX 474..488
FT /evidence="ECO:0007829|PDB:3RTA"
SQ SEQUENCE 490 AA; 53004 MW; 580917C98F8BE2FC CRC64;
MKEIDELTIK EYGVDSRILM ERAGISVVLA MEEELGNLSD YRFLVLCGGG NNGGDGFVVA
RNLLGVVKDV LVVFLGKKKT PDCEYNYGLY KKFGGKVVEQ FEPSILNEFD VVVDAIFGTG
LRGEITGEYA EIINLVNKSG KVVVSVDVPS GIDSNTGKVL RTAVKADLTV TFGVPKIGHI
LFPGRDLTGK LKVANIGHPV HLINSINRYV ITREMVRSLL PERPRDSHKG TYGKVLIIAG
SRLYSGAPVL SGMGSLKVGT GLVKLAVPFP QNLIATSRFP ELISVPIDTE KGFFSLQNLQ
ECLELSKDVD VVAIGPGLGN NEHVREFVNE FLKTLEKPAV IDADAINVLD TSVLKERKSP
AVLTPHPGEM ARLVKKTVGD VKYNYELAEE FAKENDCVLV LKSATTIVTD GEKTLFNITG
NTGLSKGGSG DVLTGMIAGF IAQGLSPLEA STVSVYLHGF AAELFEQDER GLTASELLRL
IPEAIRRLKE
