NADA_THEMA
ID NADA_THEMA Reviewed; 298 AA.
AC Q9X1X7;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Quinolinate synthase {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000303|PubMed:24650327};
DE EC=2.5.1.72 {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000269|PubMed:24650327};
GN Name=nadA {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000303|PubMed:24650327};
GN OrderedLocusNames=TM_1644;
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] {ECO:0007744|PDB:4P3X}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF MUTANT ARG-219 IN COMPLEX WITH
RP IRON-SULFUR (4FE-4S), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP MUTAGENESIS OF TYR-21 AND LYS-219.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=24650327; DOI=10.1021/ja501431b;
RA Cherrier M.V., Chan A., Darnault C., Reichmann D., Amara P.,
RA Ollagnier de Choudens S., Fontecilla-Camps J.C.;
RT "The crystal structure of FeS quinolinate synthase unravels an enzymatic
RT dehydration mechanism that uses tyrosine and a hydrolase-type triad.";
RL J. Am. Chem. Soc. 136:5253-5256(2014).
RN [3] {ECO:0007744|PDB:5F33, ECO:0007744|PDB:5F35, ECO:0007744|PDB:5F3D, ECO:0007744|PDB:5LQM, ECO:0007744|PDB:5LQS}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF MUTANTS PHE-21/ARG-219 AND
RP PHE-107/ARG-219 IN COMPLEXES WITH IRON-SULFUR (4FE-4S); SUBSTRATE ANALOGS;
RP REACTION INTERMEDIATE AND QUINOLINIC ACID, REACTION MECHANISM, COFACTOR,
RP AND MUTAGENESIS OF TYR-21; TYR-107 AND LYS-219.
RX PubMed=27545412; DOI=10.1021/jacs.6b05884;
RA Volbeda A., Darnault C., Renoux O., Reichmann D., Amara P.,
RA Ollagnier de Choudens S., Fontecilla-Camps J.C.;
RT "Crystal structures of quinolinate synthase in complex with a substrate
RT analogue, the condensation intermediate, and substrate-derived product.";
RL J. Am. Chem. Soc. 138:11802-11809(2016).
RN [4] {ECO:0007744|PDB:6F48, ECO:0007744|PDB:6F4D, ECO:0007744|PDB:6F4L, ECO:0007744|PDB:6G74}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF MUTANTS ARG-219 AND
RP PHE-21/ARG-219 IN COMPLEXES WITH IRON-SULFUR (4FE-4S); SUBSTRATE/PRODUCT
RP ANALOGS AND REACTION INTERMEDIATES, REACTION MECHANISM, AND COFACTOR.
RX PubMed=29641168; DOI=10.1021/acschembio.7b01104;
RA Volbeda A., Saez Cabodevilla J., Darnault C., Gigarel O., Han T.H.,
RA Renoux O., Hamelin O., Ollagnier-de-Choudens S., Amara P.,
RA Fontecilla-Camps J.C.;
RT "Crystallographic trapping of reaction intermediates in quinolinic acid
RT synthesis by NadA.";
RL ACS Chem. Biol. 13:1209-1217(2018).
RN [5] {ECO:0007744|PDB:6I0K, ECO:0007744|PDB:6I0P, ECO:0007744|PDB:6I0R}
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF MUTANT PHE-21/ARG-219 IN
RP COMPLEXES WITH IRON-SULFUR (4FE-4S) AND INHIBITORS, COFACTOR, AND ACTIVITY
RP REGULATION.
RX PubMed=30855610; DOI=10.1039/c8cc09023h;
RA Saez Cabodevilla J., Volbeda A., Hamelin O., Latour J.M., Gigarel O.,
RA Clemancey M., Darnault C., Reichmann D., Amara P., Fontecilla-Camps J.C.,
RA Ollagnier de Choudens S.;
RT "Design of specific inhibitors of quinolinate synthase based on [4Fe-4S]
RT cluster coordination.";
RL Chem. Commun. (Camb.) 55:3725-3728(2019).
CC -!- FUNCTION: Catalyzes the condensation of iminoaspartate with
CC dihydroxyacetone phosphate to form quinolinate. {ECO:0000255|HAMAP-
CC Rule:MF_00568, ECO:0000269|PubMed:24650327}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydroxyacetone phosphate + iminosuccinate = H(+) + 2 H2O +
CC phosphate + quinolinate; Xref=Rhea:RHEA:25888, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29959, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57642, ChEBI:CHEBI:77875; EC=2.5.1.72;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25889;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00568};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000269|PubMed:24650327, ECO:0000269|PubMed:27545412,
CC ECO:0000269|PubMed:29641168, ECO:0000269|PubMed:30855610};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00568, ECO:0000269|PubMed:24650327,
CC ECO:0000269|PubMed:27545412, ECO:0000269|PubMed:29641168,
CC ECO:0000269|PubMed:30855610};
CC -!- ACTIVITY REGULATION: Inhibited by 4,5 dithiohydroxyphthalic acid
CC (DTHPA) analogs, which bind to the catalytic iron site of the [4Fe-4S]
CC cluster. {ECO:0000269|PubMed:30855610}.
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
CC iminoaspartate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000305}.
CC -!- SIMILARITY: Belongs to the quinolinate synthase family. Type 2
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00568}.
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DR EMBL; AE000512; AAD36711.1; -; Genomic_DNA.
DR PIR; A72227; A72227.
DR RefSeq; NP_229444.1; NC_000853.1.
DR RefSeq; WP_004082140.1; NZ_CP011107.1.
DR PDB; 4P3X; X-ray; 1.65 A; A=1-298.
DR PDB; 5F33; X-ray; 1.45 A; A=1-298.
DR PDB; 5F35; X-ray; 1.60 A; A=1-298.
DR PDB; 5F3D; X-ray; 1.90 A; A=1-298.
DR PDB; 5LQM; X-ray; 1.62 A; A=1-298.
DR PDB; 5LQS; X-ray; 1.90 A; A=1-298.
DR PDB; 6F48; X-ray; 1.50 A; A=1-298.
DR PDB; 6F4D; X-ray; 2.00 A; A=1-298.
DR PDB; 6F4L; X-ray; 2.30 A; A=1-298.
DR PDB; 6G74; X-ray; 2.00 A; A/B=1-298.
DR PDB; 6I0K; X-ray; 1.64 A; A=1-298.
DR PDB; 6I0P; X-ray; 1.90 A; A=1-298.
DR PDB; 6I0R; X-ray; 2.10 A; A=1-298.
DR PDB; 7P4M; X-ray; 1.55 A; A=1-298.
DR PDB; 7P4P; X-ray; 1.75 A; A=1-298.
DR PDB; 7P4Q; X-ray; 2.20 A; A=1-298.
DR PDBsum; 4P3X; -.
DR PDBsum; 5F33; -.
DR PDBsum; 5F35; -.
DR PDBsum; 5F3D; -.
DR PDBsum; 5LQM; -.
DR PDBsum; 5LQS; -.
DR PDBsum; 6F48; -.
DR PDBsum; 6F4D; -.
DR PDBsum; 6F4L; -.
DR PDBsum; 6G74; -.
DR PDBsum; 6I0K; -.
DR PDBsum; 6I0P; -.
DR PDBsum; 6I0R; -.
DR PDBsum; 7P4M; -.
DR PDBsum; 7P4P; -.
DR PDBsum; 7P4Q; -.
DR AlphaFoldDB; Q9X1X7; -.
DR SMR; Q9X1X7; -.
DR STRING; 243274.THEMA_06025; -.
DR EnsemblBacteria; AAD36711; AAD36711; TM_1644.
DR KEGG; tma:TM1644; -.
DR eggNOG; COG0379; Bacteria.
DR InParanoid; Q9X1X7; -.
DR OMA; CFCSTMN; -.
DR OrthoDB; 613347at2; -.
DR BRENDA; 2.5.1.72; 6331.
DR UniPathway; UPA00253; UER00327.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008987; F:quinolinate synthetase A activity; IBA:GO_Central.
DR GO; GO:0034628; P:'de novo' NAD biosynthetic process from aspartate; IBA:GO_Central.
DR Gene3D; 3.40.50.10800; -; 3.
DR HAMAP; MF_00568; NadA_type2; 1.
DR InterPro; IPR003473; NadA.
DR InterPro; IPR036094; NadA_sf.
DR InterPro; IPR023066; Quinolinate_synth_type2.
DR PANTHER; PTHR30573; PTHR30573; 1.
DR Pfam; PF02445; NadA; 1.
DR SUPFAM; SSF142754; SSF142754; 1.
DR TIGRFAMs; TIGR00550; nadA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Cytoplasm; Iron; Iron-sulfur; Metal-binding;
KW Pyridine nucleotide biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..298
FT /note="Quinolinate synthase"
FT /id="PRO_0000155798"
FT BINDING 19
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168,
FT ECO:0000305|PubMed:30855610"
FT BINDING 36
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168,
FT ECO:0000305|PubMed:30855610"
FT BINDING 81
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:24650327, ECO:0000269|PubMed:27545412,
FT ECO:0000269|PubMed:29641168, ECO:0007744|PDB:4P3X,
FT ECO:0007744|PDB:5F33, ECO:0007744|PDB:5F35,
FT ECO:0007744|PDB:5F3D, ECO:0007744|PDB:5LQM,
FT ECO:0007744|PDB:5LQS"
FT BINDING 107..109
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168"
FT BINDING 124
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168,
FT ECO:0000305|PubMed:30855610"
FT BINDING 168
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:24650327, ECO:0000269|PubMed:27545412,
FT ECO:0000269|PubMed:29641168, ECO:0007744|PDB:4P3X,
FT ECO:0007744|PDB:5F33, ECO:0007744|PDB:5F35,
FT ECO:0007744|PDB:5F3D, ECO:0007744|PDB:5LQM,
FT ECO:0007744|PDB:5LQS"
FT BINDING 193..195
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168,
FT ECO:0000305|PubMed:30855610"
FT BINDING 210
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000305|PubMed:27545412, ECO:0000305|PubMed:29641168,
FT ECO:0000305|PubMed:30855610"
FT BINDING 254
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:24650327, ECO:0000269|PubMed:27545412,
FT ECO:0000269|PubMed:29641168, ECO:0007744|PDB:4P3X,
FT ECO:0007744|PDB:5F33, ECO:0007744|PDB:5F35,
FT ECO:0007744|PDB:5F3D, ECO:0007744|PDB:5LQM,
FT ECO:0007744|PDB:5LQS"
FT MUTAGEN 21
FT /note="Y->F: Retains weak activity; when associated with R-
FT 219."
FT /evidence="ECO:0000269|PubMed:24650327,
FT ECO:0000269|PubMed:27545412"
FT MUTAGEN 107
FT /note="Y->F: Loss of activity; when associated with R-219."
FT /evidence="ECO:0000269|PubMed:27545412"
FT MUTAGEN 219
FT /note="K->R: No change in activity. Retains weak activity;
FT when associated with F-21. Loss of activity; when
FT associated with F-107."
FT /evidence="ECO:0000269|PubMed:24650327,
FT ECO:0000269|PubMed:27545412"
FT HELIX 1..12
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 24..27
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 36..45
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 57..66
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 89..98
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:5F33"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 127..133
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 176..184
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 198..203
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:5F33"
FT STRAND 244..250
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:5F33"
FT HELIX 280..297
FT /evidence="ECO:0007829|PDB:5F33"
SQ SEQUENCE 298 AA; 33617 MW; 682510831BFF6D01 CRC64;
MVDEILKLKK EKGYIILAHN YQIPELQDIA DFVGDSLQLA RKAMELSEKK ILFLGVDFMA
ELVKILNPDK KVIVPDRSAT CPMANRLTPE IIREYREKFP DAPVVLYVNS TSECKTLADV
ICTSANAVEV VKKLDSSVVI FGPDRNLGEY VAEKTGKKVI TIPENGHCPV HQFNAESIDA
VRKKYPDAKV IVHPECPKPV RDKADYVGST GQMEKIPEKD PSRIFVIGTE IGMIHKLKKK
FPDREFVPLE MAVCVNMKKN TLENTLHALQ TESFEVILPK EVIEKAKKPI LRMFELMG
