HMAS_AMYOR
ID HMAS_AMYOR Reviewed; 357 AA.
AC O52791;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=4-hydroxymandelate synthase;
DE Short=HMS;
DE Short=HmaS;
DE EC=1.13.11.46;
DE AltName: Full=4-hydroxyphenylpyruvate dioxygenase II;
OS Amycolatopsis orientalis (Nocardia orientalis).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis.
OX NCBI_TaxID=31958;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RX PubMed=9545426; DOI=10.1016/s1074-5521(98)90060-6;
RA van Wageningen A., Kirkpatrick P., Williams D., Harris B., Kershaw J.,
RA Lennard N., Jones M., Jones S., Solenberg P.;
RT "Sequencing and analysis of genes involved in the biosynthesis of a
RT vancomycin group antibiotic.";
RL Chem. Biol. 5:155-162(1998).
RN [2]
RP FUNCTION IN THE BIOSYNTHESIS OF L-P-HYDROXYPHENYLGLYCINE AND AS A
RP HYDROXYMANDELATE SYNTHASE, CATALYTIC ACTIVITY, AND NOMENCLATURE.
RX PubMed=11137816; DOI=10.1016/s1074-5521(00)00043-0;
RA Hubbard B.K., Thomas M.G., Walsh C.T.;
RT "Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid
RT constituent of peptide antibiotics.";
RL Chem. Biol. 7:931-942(2000).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND METAL,
RP REACTION MECHANISM, COFACTOR, AND SUBUNIT.
RX PubMed=18215022; DOI=10.1021/bi701438r;
RA Brownlee J., He P., Moran G.R., Harrison D.H.;
RT "Two roads diverged: the structure of hydroxymandelate synthase from
RT Amycolatopsis orientalis in complex with 4-hydroxymandelate.";
RL Biochemistry 47:2002-2013(2008).
CC -!- FUNCTION: Required to synthesize hydroxyphenylglycine, a recurring
CC skeletal component of nonproteinogenic macrocyclic peptide antibiotics
CC such as vancomycin. Catalyzes the conversion of p-hydroxyphenylpyruvate
CC to p-hydroxymandelate. The decarboxylation and hydroxylation activities
CC of HmaS show novel and distinct regioselectivity, compared to all other
CC known p-hydroxyphenylpyruvate dioxygenases, by hydroxylating the
CC benzylic position of the substrate instead of the phenyl ring.
CC {ECO:0000269|PubMed:11137816}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(4-hydroxyphenyl)pyruvate + O2 = (S)-4-hydroxymandelate +
CC CO2; Xref=Rhea:RHEA:21376, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17210, ChEBI:CHEBI:36242; EC=1.13.11.46;
CC Evidence={ECO:0000269|PubMed:11137816};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:18215022};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000269|PubMed:18215022};
CC -!- PATHWAY: Antibiotic biosynthesis; vancomycin biosynthesis.
CC {ECO:0000269|PubMed:9545426}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18215022}.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
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DR EMBL; AJ223998; CAA11761.1; -; Genomic_DNA.
DR PIR; T17470; T17470.
DR PDB; 2R5V; X-ray; 2.30 A; A/B=1-357.
DR PDBsum; 2R5V; -.
DR AlphaFoldDB; O52791; -.
DR SMR; O52791; -.
DR DrugBank; DB07896; (2S)-hydroxy(4-hydroxyphenyl)ethanoic acid.
DR KEGG; ag:CAA11761; -.
DR BRENDA; 1.1.3.46; 315.
DR UniPathway; UPA00162; -.
DR EvolutionaryTrace; O52791; -.
DR GO; GO:0050585; F:4-hydroxymandelate synthase activity; IDA:UniProtKB.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0009072; P:aromatic amino acid family metabolic process; IEA:InterPro.
DR GO; GO:0033072; P:vancomycin biosynthetic process; IDA:UniProtKB.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR PANTHER; PTHR11959; PTHR11959; 1.
DR Pfam; PF00903; Glyoxalase; 1.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR01263; 4HPPD; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Iron; Metal-binding; Oxidoreductase;
KW Repeat.
FT CHAIN 1..357
FT /note="4-hydroxymandelate synthase"
FT /id="PRO_0000418534"
FT DOMAIN 5..129
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 158..309
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 161
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 161
FT /ligand="substrate"
FT BINDING 201
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18215022"
FT BINDING 214
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18215022"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18215022"
FT BINDING 305
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18215022"
FT BINDING 320
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 30..37
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 50..59
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 72..83
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 85..94
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 158..165
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 171..182
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 185..194
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 197..205
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 212..218
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 226..234
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 236..245
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 268..272
FT /evidence="ECO:0007829|PDB:2R5V"
FT TURN 273..277
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 301..308
FT /evidence="ECO:0007829|PDB:2R5V"
FT STRAND 318..326
FT /evidence="ECO:0007829|PDB:2R5V"
FT HELIX 332..347
FT /evidence="ECO:0007829|PDB:2R5V"
SQ SEQUENCE 357 AA; 38339 MW; F146FCE537CEF2CA CRC64;
MQNFEIDYVE MYVENLEVAA FSWVDKYAFA VAGTSRSADH RSIALRQGQV TLVLTEPTSD
RHPAAAYLQT HGDGVADIAM ATSDVAAAYE AAVRAGAEAV RAPGQHSEAA VTTATIGGFG
DVVHTLIQRD GTSAELPPGF TGSMDVTNHG KGDVDLLGID HFAICLNAGD LGPTVEYYER
ALGFRQIFDE HIVVGAQAMN STVVQSASGA VTLTLIEPDR NADPGQIDEF LKDHQGAGVQ
HIAFNSNDAV RAVKALSERG VEFLKTPGAY YDLLGERITL QTHSLDDLRA TNVLADEDHG
GQLFQIFTAS THPRHTIFFE VIERQGAGTF GSSNIKALYE AVELERTGQS EFGAARR
