ID 3HAO_CUPMC Reviewed; 174 AA. AC Q1LCS4; DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2006, sequence version 1. DT 27-MAR-2024, entry version 113. DE RecName: Full=3-hydroxyanthranilate 3,4-dioxygenase {ECO:0000255|HAMAP-Rule:MF_00825}; DE EC=1.13.11.6 {ECO:0000255|HAMAP-Rule:MF_00825}; DE AltName: Full=3-hydroxyanthranilate oxygenase {ECO:0000255|HAMAP-Rule:MF_00825}; DE Short=3-HAO {ECO:0000255|HAMAP-Rule:MF_00825}; DE AltName: Full=3-hydroxyanthranilic acid dioxygenase {ECO:0000255|HAMAP-Rule:MF_00825}; DE Short=HAD {ECO:0000255|HAMAP-Rule:MF_00825}; GN Name=nbaC {ECO:0000255|HAMAP-Rule:MF_00825}; GN OrderedLocusNames=Rmet_5193; OS Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / OS CH34) (Ralstonia metallidurans). OG Plasmid megaplasmid. OC Bacteria; Pseudomonadota; Betaproteobacteria; Burkholderiales; OC Burkholderiaceae; Cupriavidus. OX NCBI_TaxID=266264; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 43123 / DSM 2839 / NBRC 102507 / CH34; RX PubMed=20463976; DOI=10.1371/journal.pone.0010433; RA Janssen P.J., Van Houdt R., Moors H., Monsieurs P., Morin N., Michaux A., RA Benotmane M.A., Leys N., Vallaeys T., Lapidus A., Monchy S., Medigue C., RA Taghavi S., McCorkle S., Dunn J., van der Lelie D., Mergeay M.; RT "The complete genome sequence of Cupriavidus metallidurans strain CH34, a RT master survivalist in harsh and anthropogenic environments."; RL PLoS ONE 5:E10433-E10433(2010). RN [2] RP FUNCTION, ACTIVITY REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15909977; DOI=10.1021/bi0473455; RA Colabroy K.L., Zhai H., Li T., Ge Y., Zhang Y., Liu A., Ealick S.E., RA McLafferty F.W., Begley T.P.; RT "The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by RT 4-chloro-3-hydroxyanthranilate."; RL Biochemistry 44:7623-7631(2005). RN [3] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF NATIVE PROTEIN AND COMPLEXES WITH RP SUBSTRATES OR INHIBITOR AND IRON, COFACTOR, KINETIC PARAMETERS, MUTAGENESIS RP OF ARG-47; ARG-99 AND GLU-110, SUBUNIT, AND REACTION MECHANISM. RX PubMed=15909978; DOI=10.1021/bi047353l; RA Zhang Y., Colabroy K.L., Begley T.P., Ealick S.E.; RT "Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic RT mechanism of a complex oxidation involved in NAD biosynthesis."; RL Biochemistry 44:7632-7643(2005). CC -!- FUNCTION: Catalyzes the oxidative ring opening of 3-hydroxyanthranilate CC to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes CC to quinolinate. {ECO:0000255|HAMAP-Rule:MF_00825, CC ECO:0000269|PubMed:15909977}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate CC 6-semialdehyde; Xref=Rhea:RHEA:17953, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:36559, ChEBI:CHEBI:77612; EC=1.13.11.6; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00825}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00825, ECO:0000269|PubMed:15909978}; CC Note=Binds 2 Fe(2+) ions per subunit. {ECO:0000255|HAMAP-Rule:MF_00825, CC ECO:0000269|PubMed:15909978}; CC -!- ACTIVITY REGULATION: Inhibited by 4-chloro-3-hydroxyanthranilate. CC Mechanism of inactivation involves the oxidation of the catalytic CC active site Fe(2+) to the catalytically inactive Fe(3+) oxidation CC state, superoxide production, and formation of two disulfide bonds CC between Cys-125 and Cys-128, and Cys-162 and Cys-165. Enzyme can be CC reactivated under reducing conditions. {ECO:0000269|PubMed:15909977}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=22.4 uM for 3-hydroxyanthranilate {ECO:0000269|PubMed:15909978}; CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from CC L-kynurenine: step 3/3. {ECO:0000255|HAMAP-Rule:MF_00825}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00825, CC ECO:0000269|PubMed:15909978}. CC -!- SIMILARITY: Belongs to the 3-HAO family. {ECO:0000255|HAMAP- CC Rule:MF_00825}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000353; ABF12052.1; -; Genomic_DNA. DR RefSeq; WP_011519599.1; NC_007974.2. DR PDB; 1YFU; X-ray; 1.90 A; A=1-174. DR PDB; 1YFW; X-ray; 2.00 A; A=1-174. DR PDB; 1YFX; X-ray; 2.00 A; A=1-174. DR PDB; 1YFY; X-ray; 3.20 A; A=1-174. DR PDB; 4HSJ; X-ray; 1.88 A; A=1-174. DR PDB; 4HSL; X-ray; 2.00 A; A=1-174. DR PDB; 4HVO; X-ray; 1.75 A; A=1-174. DR PDB; 4HVQ; X-ray; 2.81 A; A=1-154. DR PDB; 4HVR; X-ray; 2.70 A; A=1-174. DR PDB; 4I3P; X-ray; 1.96 A; A=1-174. DR PDB; 4L2N; X-ray; 1.74 A; A=1-174. DR PDB; 4R52; X-ray; 1.53 A; A=1-174. DR PDB; 4WZC; X-ray; 1.84 A; A=1-174. DR PDB; 5V26; X-ray; 1.79 A; A/B=1-174. DR PDB; 5V27; X-ray; 2.35 A; A=1-174. DR PDB; 5V28; X-ray; 2.72 A; A=1-174. DR PDB; 6BVP; X-ray; 1.90 A; A=1-174. DR PDB; 6BVQ; X-ray; 2.08 A; A=1-174. DR PDB; 6BVR; X-ray; 1.90 A; A=1-174. DR PDB; 6BVS; X-ray; 2.32 A; A=1-174. DR PDB; 6CD3; X-ray; 2.61 A; A=1-174. DR PDB; 6D60; X-ray; 2.22 A; A=1-174. DR PDB; 6D61; X-ray; 1.74 A; A=1-174. DR PDB; 6D62; X-ray; 1.77 A; A=1-174. DR PDB; 6VI5; X-ray; 1.60 A; A=1-174. DR PDB; 6VI6; X-ray; 1.90 A; A=1-174. DR PDB; 6VI7; X-ray; 2.62 A; A=1-174. DR PDB; 6VI8; X-ray; 1.95 A; A=1-174. DR PDB; 6VI9; X-ray; 2.31 A; A=1-174. DR PDB; 6VIA; X-ray; 1.59 A; A=1-174. DR PDB; 6VIB; X-ray; 1.84 A; A=1-174. DR PDB; 6X11; X-ray; 2.10 A; A=1-174. DR PDBsum; 1YFU; -. DR PDBsum; 1YFW; -. DR PDBsum; 1YFX; -. DR PDBsum; 1YFY; -. DR PDBsum; 4HSJ; -. DR PDBsum; 4HSL; -. DR PDBsum; 4HVO; -. DR PDBsum; 4HVQ; -. DR PDBsum; 4HVR; -. DR PDBsum; 4I3P; -. DR PDBsum; 4L2N; -. DR PDBsum; 4R52; -. DR PDBsum; 4WZC; -. DR PDBsum; 5V26; -. DR PDBsum; 5V27; -. DR PDBsum; 5V28; -. DR PDBsum; 6BVP; -. DR PDBsum; 6BVQ; -. DR PDBsum; 6BVR; -. DR PDBsum; 6BVS; -. DR PDBsum; 6CD3; -. DR PDBsum; 6D60; -. DR PDBsum; 6D61; -. DR PDBsum; 6D62; -. DR PDBsum; 6VI5; -. DR PDBsum; 6VI6; -. DR PDBsum; 6VI7; -. DR PDBsum; 6VI8; -. DR PDBsum; 6VI9; -. DR PDBsum; 6VIA; -. DR PDBsum; 6VIB; -. DR PDBsum; 6X11; -. DR AlphaFoldDB; Q1LCS4; -. DR SMR; Q1LCS4; -. DR DrugBank; DB04598; 2-AMINO-4-CHLORO-3-HYDROXYBENZOIC ACID. DR KEGG; rme:Rmet_5193; -. DR eggNOG; COG1917; Bacteria. DR HOGENOM; CLU_095765_0_0_4; -. DR SABIO-RK; Q1LCS4; -. DR UniPathway; UPA00253; UER00330. DR EvolutionaryTrace; Q1LCS4; -. DR Proteomes; UP000002429; Plasmid megaplasmid CH34. DR GO; GO:0000334; F:3-hydroxyanthranilate 3,4-dioxygenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0008198; F:ferrous iron binding; IEA:UniProtKB-UniRule. DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule. DR GO; GO:0043420; P:anthranilate metabolic process; IEA:UniProtKB-UniRule. DR GO; GO:0019805; P:quinolinate biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0006569; P:tryptophan catabolic process; IEA:UniProtKB-UniRule. DR CDD; cd06123; cupin_HAO; 1. DR Gene3D; 2.60.120.10; Jelly Rolls; 1. DR HAMAP; MF_00825; 3_HAO; 1. DR InterPro; IPR010329; 3hydroanth_dOase. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR011051; RmlC_Cupin_sf. DR NCBIfam; TIGR03037; anthran_nbaC; 1. DR PANTHER; PTHR15497; 3-HYDROXYANTHRANILATE 3,4-DIOXYGENASE; 1. DR PANTHER; PTHR15497:SF1; 3-HYDROXYANTHRANILATE 3,4-DIOXYGENASE; 1. DR Pfam; PF06052; 3-HAO; 1. DR SUPFAM; SSF51182; RmlC-like cupins; 1. PE 1: Evidence at protein level; KW 3D-structure; Dioxygenase; Iron; Metal-binding; Oxidoreductase; Plasmid; KW Pyridine nucleotide biosynthesis; Reference proteome. FT CHAIN 1..174 FT /note="3-hydroxyanthranilate 3,4-dioxygenase" FT /id="PRO_0000245477" FT BINDING 47 FT /ligand="O2" FT /ligand_id="ChEBI:CHEBI:15379" FT BINDING 51 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 57 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 57 FT /ligand="substrate" FT BINDING 95 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 99 FT /ligand="substrate" FT BINDING 110 FT /ligand="substrate" FT BINDING 125 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 128 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 162 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 165 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT MUTAGEN 47 FT /note="R->A: Increases KM for 3-hydroxyanthranilate 7-fold. FT Decreases activity 1000-fold." FT /evidence="ECO:0000269|PubMed:15909978" FT MUTAGEN 99 FT /note="R->A: Increases KM for 3-hydroxyanthranilate FT 40-fold. Decreases activity 5000-fold." FT /evidence="ECO:0000269|PubMed:15909978" FT MUTAGEN 110 FT /note="E->A: Decreases KM for 3-hydroxyanthranilate 2-fold. FT Decreases activity 2000-fold." FT /evidence="ECO:0000269|PubMed:15909978" FT HELIX 10..16 FT /evidence="ECO:0007829|PDB:4R52" FT HELIX 18..20 FT /evidence="ECO:0007829|PDB:4R52" FT TURN 23..25 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 27..33 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 35..41 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:6VIA" FT STRAND 50..52 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 57..64 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 66..72 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 75..81 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 95..99 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 119..124 FT /evidence="ECO:0007829|PDB:4R52" FT TURN 126..128 FT /evidence="ECO:0007829|PDB:4R52" FT STRAND 131..137 FT /evidence="ECO:0007829|PDB:4R52" FT HELIX 142..145 FT /evidence="ECO:0007829|PDB:4R52" FT HELIX 147..154 FT /evidence="ECO:0007829|PDB:4R52" FT HELIX 157..160 FT /evidence="ECO:0007829|PDB:4R52" FT TURN 163..165 FT /evidence="ECO:0007829|PDB:4R52" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:1YFW" SQ SEQUENCE 174 AA; 20028 MW; 385F2E3DEB3947B8 CRC64; MLTYGAPFNF PRWIDEHAHL LKPPVGNRQV WQDSDFIVTV VGGPNHRTDY HDDPLEEFFY QLRGNAYLNL WVDGRRERAD LKEGDIFLLP PHVRHSPQRP EAGSACLVIE RQRPAGMLDG FEWYCDACGH LVHRVEVQLK SIVTDLPPLF ESFYASEDKR RCPHCGQVHP GRAA //