NADA_PYRHO
ID NADA_PYRHO Reviewed; 300 AA.
AC O57767;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Quinolinate synthase {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000303|PubMed:15937336};
DE Short=QS {ECO:0000303|PubMed:15937336};
DE EC=2.5.1.72 {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000269|PubMed:15937336, ECO:0000269|PubMed:27224840};
GN Name=nadA {ECO:0000255|HAMAP-Rule:MF_00568, ECO:0000303|PubMed:15937336};
GN OrderedLocusNames=PH0013;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2] {ECO:0007744|PDB:1WZU}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, PATHWAY, AND SUBUNIT.
RX PubMed=15937336; DOI=10.1074/jbc.c500192200;
RA Sakuraba H., Tsuge H., Yoneda K., Katunuma N., Ohshima T.;
RT "Crystal structure of the NAD biosynthetic enzyme quinolinate synthase.";
RL J. Biol. Chem. 280:26645-26648(2005).
RN [3] {ECO:0007744|PDB:4ZK6}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR (4FE-4S)
RP AND QUINOLINIC ACID, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF TYR-23; TYR-109;
RP ASN-111 AND GLU-198.
RX PubMed=27224840; DOI=10.1021/jacs.6b02708;
RA Esakova O.A., Silakov A., Grove T.L., Saunders A.H., McLaughlin M.I.,
RA Yennawar N.H., Booker S.J.;
RT "Structure of quinolinate synthase from Pyrococcus horikoshii in the
RT presence of its product, quinolinic acid.";
RL J. Am. Chem. Soc. 138:7224-7227(2016).
RN [4] {ECO:0007744|PDB:5KTM, ECO:0007744|PDB:5KTN, ECO:0007744|PDB:5KTO, ECO:0007744|PDB:5KTP, ECO:0007744|PDB:5KTR, ECO:0007744|PDB:5KTS, ECO:0007744|PDB:5KTT}
RP X-RAY CRYSTALLOGRAPHY (1.34 ANGSTROMS) IN COMPLEXES WITH IRON-SULFUR
RP (4FE-4S); SUBSTRATE ANALOGS; DIHYDROXYACETONE PHOSPHATE AND QUINOLINATE,
RP COFACTOR, AND DOMAIN.
RX PubMed=27404889; DOI=10.1021/acs.biochem.6b00626;
RA Fenwick M.K., Ealick S.E.;
RT "Crystal structures of the iron-sulfur cluster-dependent quinolinate
RT synthase in complex with dihydroxyacetone phosphate, iminoaspartate
RT analogues, and quinolinate.";
RL Biochemistry 55:4135-4139(2016).
RN [5] {ECO:0007744|PDB:6NSO, ECO:0007744|PDB:6NSU, ECO:0007744|PDB:6OR8, ECO:0007744|PDB:6ORA}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF WILD-TYPE IN COMPLEXES WITH
RP IRON-SULFUR (4FE-4S); IMINOSUCCINATE; DIHYDROXYACETONE PHOSPHATE AND
RP REACTION INTERMEDIATE AND OF MUTANT GLN-198 IN COMPLEX WITH IRON-SULFUR
RP (4FE-4S) AND REACTION INTERMEDIATE, REACTION MECHANISM, AND COFACTOR.
RX PubMed=31390192; DOI=10.1021/jacs.9b02513;
RA Esakova O.A., Silakov A., Grove T.L., Warui D.M., Yennawar N.H.,
RA Booker S.J.;
RT "An unexpected species determined by X-ray crystallography that may
RT represent an intermediate in the reaction catalyzed by quinolinate
RT synthase.";
RL J. Am. Chem. Soc. 141:14142-14151(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:15937336,
CC ECO:0000269|PubMed:27224840}.
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 ECO:0000269|PubMed:15937336, ECO:0000269|PubMed:27224840};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25889;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000269|PubMed:15937336};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000269|PubMed:27224840, ECO:0000269|PubMed:27404889,
CC ECO:0000269|PubMed:31390192};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00568, ECO:0000269|PubMed:27224840,
CC ECO:0000269|PubMed:27404889, ECO:0000269|PubMed:31390192};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.24 mM for dihydroxyacetone phosphate
CC {ECO:0000269|PubMed:27224840};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
CC iminoaspartate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00568,
CC ECO:0000305|PubMed:15937336}.
CC -!- SUBUNIT: Monomer (PubMed:15937336). Homodimer (PubMed:27224840).
CC {ECO:0000269|PubMed:15937336, ECO:0000269|PubMed:27224840}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00568}.
CC -!- DOMAIN: Contains three domains displaying pseudo-three-fold symmetry
CC that each contribute a cysteine residue for ligation to a centrally
CC located [4Fe-4S] cluster. {ECO:0000269|PubMed:27404889}.
CC -!- SIMILARITY: Belongs to the quinolinate synthase family. Type 2
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00568}.
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DR EMBL; BA000001; BAA29081.1; -; Genomic_DNA.
DR PIR; B71219; B71219.
DR RefSeq; WP_010884133.1; NC_000961.1.
DR PDB; 1WZU; X-ray; 2.00 A; A=1-300.
DR PDB; 4ZK6; X-ray; 1.90 A; A/B=1-300.
DR PDB; 5KTM; X-ray; 1.44 A; A=1-300.
DR PDB; 5KTN; X-ray; 1.34 A; A=1-300.
DR PDB; 5KTO; X-ray; 1.44 A; A=1-300.
DR PDB; 5KTP; X-ray; 1.54 A; A=1-300.
DR PDB; 5KTR; X-ray; 1.34 A; A=1-300.
DR PDB; 5KTS; X-ray; 1.34 A; A=1-300.
DR PDB; 5KTT; X-ray; 1.50 A; A=1-300.
DR PDB; 6NSO; X-ray; 1.60 A; A=1-300.
DR PDB; 6NSU; X-ray; 2.15 A; A=1-300.
DR PDB; 6OR8; X-ray; 1.65 A; A=1-300.
DR PDB; 6ORA; X-ray; 2.20 A; A/B=1-300.
DR PDBsum; 1WZU; -.
DR PDBsum; 4ZK6; -.
DR PDBsum; 5KTM; -.
DR PDBsum; 5KTN; -.
DR PDBsum; 5KTO; -.
DR PDBsum; 5KTP; -.
DR PDBsum; 5KTR; -.
DR PDBsum; 5KTS; -.
DR PDBsum; 5KTT; -.
DR PDBsum; 6NSO; -.
DR PDBsum; 6NSU; -.
DR PDBsum; 6OR8; -.
DR PDBsum; 6ORA; -.
DR AlphaFoldDB; O57767; -.
DR SMR; O57767; -.
DR STRING; 70601.3256398; -.
DR EnsemblBacteria; BAA29081; BAA29081; BAA29081.
DR GeneID; 1443915; -.
DR KEGG; pho:PH0013; -.
DR eggNOG; arCOG04459; Archaea.
DR OMA; CFCSTMN; -.
DR OrthoDB; 18897at2157; -.
DR BRENDA; 2.5.1.72; 5244.
DR UniPathway; UPA00253; UER00327.
DR EvolutionaryTrace; O57767; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008987; F:quinolinate synthetase A activity; IEA:UniProtKB-UniRule.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniRule.
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; Transferase.
FT CHAIN 1..300
FT /note="Quinolinate synthase"
FT /id="PRO_0000155810"
FT BINDING 21
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27224840, ECO:0000305|PubMed:27404889"
FT BINDING 38
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27224840, ECO:0000305|PubMed:27404889"
FT BINDING 83
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:27224840, ECO:0000269|PubMed:27404889,
FT ECO:0000269|PubMed:31390192, ECO:0007744|PDB:4ZK6,
FT ECO:0007744|PDB:5KTM, ECO:0007744|PDB:5KTN,
FT ECO:0007744|PDB:5KTO, ECO:0007744|PDB:5KTP,
FT ECO:0007744|PDB:5KTR, ECO:0007744|PDB:5KTS,
FT ECO:0007744|PDB:5KTT"
FT BINDING 109..111
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27224840, ECO:0000305|PubMed:27404889"
FT BINDING 126
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27404889"
FT BINDING 170
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:27224840, ECO:0000269|PubMed:27404889,
FT ECO:0000269|PubMed:31390192, ECO:0007744|PDB:4ZK6,
FT ECO:0007744|PDB:5KTM, ECO:0007744|PDB:5KTN,
FT ECO:0007744|PDB:5KTO, ECO:0007744|PDB:5KTP,
FT ECO:0007744|PDB:5KTR, ECO:0007744|PDB:5KTS,
FT ECO:0007744|PDB:5KTT"
FT BINDING 196..198
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27404889"
FT BINDING 213
FT /ligand="iminosuccinate"
FT /ligand_id="ChEBI:CHEBI:77875"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:31390192, ECO:0000305|PubMed:15937336,
FT ECO:0000305|PubMed:27404889"
FT BINDING 256
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00568,
FT ECO:0000269|PubMed:27224840, ECO:0000269|PubMed:27404889,
FT ECO:0000269|PubMed:31390192, ECO:0007744|PDB:4ZK6,
FT ECO:0007744|PDB:5KTM, ECO:0007744|PDB:5KTN,
FT ECO:0007744|PDB:5KTO, ECO:0007744|PDB:5KTP,
FT ECO:0007744|PDB:5KTR, ECO:0007744|PDB:5KTS,
FT ECO:0007744|PDB:5KTT"
FT MUTAGEN 23
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27224840"
FT MUTAGEN 109
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27224840"
FT MUTAGEN 111
FT /note="N->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27224840"
FT MUTAGEN 198
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27224840"
FT HELIX 3..13
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:5KTO"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 59..68
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:5KTN"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 129..135
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 233..241
FT /evidence="ECO:0007829|PDB:5KTN"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:5KTN"
FT HELIX 282..298
FT /evidence="ECO:0007829|PDB:5KTN"
SQ SEQUENCE 300 AA; 34136 MW; 35C27FD410C343E5 CRC64;
MDLVEEILRL KEERNAIILA HNYQLPEVQD IADFIGDSLE LARRATRVDA DVIVFAGVDF
MAETAKILNP DKVVLIPSRE ATCAMANMLK VEHILEAKRK YPNAPVVLYV NSTAEAKAYA
DVTVTSANAV EVVKKLDSDV VIFGPDKNLA HYVAKMTGKK IIPVPSKGHC YVHQKFTLDD
VERAKKLHPN AKLMIHPECI PEVQEKADII ASTGGMIKRA CEWDEWVVFT EREMVYRLRK
LYPQKKFYPA REDAFCIGMK AITLKNIYES LKDMKYKVEV PEEIARKARK AIERMLEMSK
