HGD_PSEPK
ID HGD_PSEPK Reviewed; 433 AA.
AC Q88E47;
DT 06-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Homogentisate 1,2-dioxygenase {ECO:0000255|HAMAP-Rule:MF_00334};
DE Short=HGDO {ECO:0000255|HAMAP-Rule:MF_00334};
DE EC=1.13.11.5 {ECO:0000255|HAMAP-Rule:MF_00334};
DE AltName: Full=Homogentisate oxygenase {ECO:0000255|HAMAP-Rule:MF_00334};
DE AltName: Full=Homogentisic acid oxidase {ECO:0000255|HAMAP-Rule:MF_00334};
DE AltName: Full=Homogentisicase {ECO:0000255|HAMAP-Rule:MF_00334};
GN Name=hmgA {ECO:0000255|HAMAP-Rule:MF_00334}; OrderedLocusNames=PP_4621;
OS Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950
OS / KT2440).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=160488;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440;
RX PubMed=12534463; DOI=10.1046/j.1462-2920.2002.00366.x;
RA Nelson K.E., Weinel C., Paulsen I.T., Dodson R.J., Hilbert H.,
RA Martins dos Santos V.A.P., Fouts D.E., Gill S.R., Pop M., Holmes M.,
RA Brinkac L.M., Beanan M.J., DeBoy R.T., Daugherty S.C., Kolonay J.F.,
RA Madupu R., Nelson W.C., White O., Peterson J.D., Khouri H.M., Hance I.,
RA Chris Lee P., Holtzapple E.K., Scanlan D., Tran K., Moazzez A.,
RA Utterback T.R., Rizzo M., Lee K., Kosack D., Moestl D., Wedler H.,
RA Lauber J., Stjepandic D., Hoheisel J., Straetz M., Heim S., Kiewitz C.,
RA Eisen J.A., Timmis K.N., Duesterhoeft A., Tuemmler B., Fraser C.M.;
RT "Complete genome sequence and comparative analysis of the metabolically
RT versatile Pseudomonas putida KT2440.";
RL Environ. Microbiol. 4:799-808(2002).
RN [2]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=U;
RX PubMed=15262943; DOI=10.1128/jb.186.15.5062-5077.2004;
RA Arias-Barrau E., Olivera E.R., Luengo J.M., Fernandez C., Galan B.,
RA Garcia J.L., Diaz E., Minambres B.;
RT "The homogentisate pathway: a central catabolic pathway involved in the
RT degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in
RT Pseudomonas putida.";
RL J. Bacteriol. 186:5062-5077(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH HOMOGENTISATE AND
RP IRON IONS, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-288 AND
RP TYR-346, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, REACTION
RP MECHANISM, AND SUBUNIT.
RX PubMed=23858455; DOI=10.1073/pnas.1302144110;
RA Jeoung J.H., Bommer M., Lin T.Y., Dobbek H.;
RT "Visualizing the substrate-, superoxo-, alkylperoxo-, and product-bound
RT states at the nonheme Fe(II) site of homogentisate dioxygenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:12625-12630(2013).
CC -!- FUNCTION: Involved in the catabolism of homogentisate (2,5-
CC dihydroxyphenylacetate or 2,5-OH-PhAc), a central intermediate in the
CC degradation of phenylalanine and tyrosine. Catalyzes the oxidative ring
CC cleavage of the ar omatic ring of 2,5-dihydroxyphenylacetate to yield
CC maleylacetoacetate. {ECO:0000269|PubMed:15262943,
CC ECO:0000269|PubMed:23858455}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=homogentisate + O2 = 4-maleylacetoacetate + H(+);
CC Xref=Rhea:RHEA:15449, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16169, ChEBI:CHEBI:17105; EC=1.13.11.5;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00334,
CC ECO:0000269|PubMed:23858455};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00334,
CC ECO:0000269|PubMed:23858455};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=53.2 uM for homogentisate {ECO:0000269|PubMed:15262943,
CC ECO:0000269|PubMed:23858455};
CC Vmax=99.4 umol/min/mg enzyme {ECO:0000269|PubMed:15262943,
CC ECO:0000269|PubMed:23858455};
CC Note=kcat is 79.5 sec(-1) for the oxidative ring cleavage of
CC homogentisate.;
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:15262943, ECO:0000269|PubMed:23858455};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 4/6.
CC {ECO:0000255|HAMAP-Rule:MF_00334}.
CC -!- SUBUNIT: Hexamer; dimer of trimers. {ECO:0000255|HAMAP-Rule:MF_00334,
CC ECO:0000269|PubMed:23858455}.
CC -!- INDUCTION: Induced by homogentisate and repressed by HmgR.
CC -!- SIMILARITY: Belongs to the homogentisate dioxygenase family.
CC {ECO:0000255|HAMAP-Rule:MF_00334}.
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DR EMBL; AE015451; AAN70194.1; -; Genomic_DNA.
DR RefSeq; NP_746730.1; NC_002947.4.
DR RefSeq; WP_010955283.1; NC_002947.4.
DR PDB; 3ZDS; X-ray; 1.70 A; A/B/C/D/E/F/G/H/I/J/K/L=1-433.
DR PDB; 4AQ2; X-ray; 1.95 A; A/B/C/D/E/F/G/H/I/J/K/L=1-433.
DR PDB; 4AQ6; X-ray; 1.98 A; A/B/C/D/E/F/G/H/I/J/K/L=1-433.
DR PDBsum; 3ZDS; -.
DR PDBsum; 4AQ2; -.
DR PDBsum; 4AQ6; -.
DR AlphaFoldDB; Q88E47; -.
DR SMR; Q88E47; -.
DR STRING; 160488.PP_4621; -.
DR EnsemblBacteria; AAN70194; AAN70194; PP_4621.
DR KEGG; ppu:PP_4621; -.
DR PATRIC; fig|160488.4.peg.4927; -.
DR eggNOG; COG3508; Bacteria.
DR HOGENOM; CLU_027174_0_0_6; -.
DR OMA; FMFETRW; -.
DR PhylomeDB; Q88E47; -.
DR BioCyc; PPUT160488:G1G01-4932-MON; -.
DR BRENDA; 1.13.11.5; 5092.
DR UniPathway; UPA00139; UER00339.
DR Proteomes; UP000000556; Chromosome.
DR GO; GO:0032993; C:protein-DNA complex; IPI:CollecTF.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IPI:CollecTF.
DR GO; GO:0004411; F:homogentisate 1,2-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IPI:CollecTF.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CollecTF.
DR GO; GO:0006572; P:tyrosine catabolic process; IDA:UniProtKB.
DR Gene3D; 2.60.120.10; -; 1.
DR HAMAP; MF_00334; Homogentis_dioxygen; 1.
DR InterPro; IPR005708; Homogentis_dOase.
DR InterPro; IPR022950; Homogentis_dOase_bac.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR11056; PTHR11056; 1.
DR Pfam; PF04209; HgmA; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
DR TIGRFAMs; TIGR01015; hmgA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Oxidoreductase;
KW Phenylalanine catabolism; Reference proteome; Tyrosine catabolism.
FT CHAIN 1..433
FT /note="Homogentisate 1,2-dioxygenase"
FT /id="PRO_0000220250"
FT ACT_SITE 288
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00334,
FT ECO:0000269|PubMed:23858455"
FT BINDING 331
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 337
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 346
FT /ligand="homogentisate"
FT /ligand_id="ChEBI:CHEBI:16169"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00334,
FT ECO:0000269|PubMed:23858455"
FT BINDING 367
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 367
FT /ligand="homogentisate"
FT /ligand_id="ChEBI:CHEBI:16169"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00334,
FT ECO:0000269|PubMed:23858455"
FT MUTAGEN 288
FT /note="H->F: Reduces the catalytic efficiency 75-fold."
FT /evidence="ECO:0000269|PubMed:23858455"
FT MUTAGEN 346
FT /note="Y->F: Decreases the affinity for homogentisate more
FT than 60-fold and reduces the catalytic efficiency 20-fold."
FT /evidence="ECO:0000269|PubMed:23858455"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3ZDS"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 128..138
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 236..245
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 248..256
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 261..267
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 281..287
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 291..294
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 308..314
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 330..344
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 358..361
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 371..379
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 391..399
FT /evidence="ECO:0007829|PDB:3ZDS"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:4AQ2"
FT HELIX 405..409
FT /evidence="ECO:0007829|PDB:3ZDS"
FT HELIX 417..421
FT /evidence="ECO:0007829|PDB:3ZDS"
SQ SEQUENCE 433 AA; 48011 MW; 6D5F4C7F91BE4512 CRC64;
MNRDTSPDLH YLSGFGNEFA SEALPGALPV GQNSPQKAPY GLYAELLSGT AFTMARSELR
RTWLYRIRPS ALHPRFERLA RQPLGGPLGG INPNRLRWSP QPIPAEPTDF IEGWLPMAAN
AGAEKPAGVS IYIYRANRSM ERVFFNADGE LLLVPEQGRL RIATELGVME VEPLEIAVIP
RGMKFRVELL DGQARGYIAE NHGAPLRLPD LGPIGSNGLA NPRDFLTPVA HYEEAEGPVQ
LVQKFLGEHW ACELQHSPLD VVAWHGSNVP YKYDLRRFNT IGTVSFDHPD PSIFTVLTSP
TSVHGMANMD FVIFPPRWMV AENTFRPPWF HRNLMNEFMG LINGAYDAKA EGFLPGGASL
HGVMSAHGPD AETCEKAIAA DLAPHKIDNT MAFMFETSQV LRPSLQALEC PQLQADYDSC
WATLPSTFNP NRR
