HPPE_STRWE
ID HPPE_STRWE Reviewed; 198 AA.
AC Q56185;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=(S)-2-hydroxypropylphosphonic acid epoxidase;
DE EC=1.11.1.23 {ECO:0000269|PubMed:16015285};
DE AltName: Full=Fosfomycin biosynthesis protein 4;
DE AltName: Full=Hydroxypropylphosphonate epoxidase;
DE Short=Sw-hppE;
GN Name=hppE; Synonyms=fom4;
OS Streptomyces wedmorensis.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=43759;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7500951; DOI=10.1007/bf00290527;
RA Hidaka T., Goda M., Kuzuyama T., Takei N., Hidaka M., Seto H.;
RT "Cloning and nucleotide sequence of fosfomycin biosynthetic genes of
RT Streptomyces wedmorensis.";
RL Mol. Gen. Genet. 249:274-280(1995).
RN [2]
RP PHOSPHINOTHRICIN TRIPEPTIDE AND FOSFOMYCIN BIOSYNTHESIS, AND PATHWAY.
RX PubMed=19516340; DOI=10.1038/nature07972;
RA Cicchillo R.M., Zhang H., Blodgett J.A., Whitteck J.T., Li G., Nair S.K.,
RA van der Donk W.A., Metcalf W.W.;
RT "An unusual carbon-carbon bond cleavage reaction during phosphinothricin
RT biosynthesis.";
RL Nature 459:871-874(2009).
RN [3] {ECO:0007744|PDB:1ZZ6, ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8, ECO:0007744|PDB:1ZZ9, ECO:0007744|PDB:1ZZB, ECO:0007744|PDB:1ZZC}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COBALT AND
RP (S)-2-HYDROXYPROPYLPHOSPHONATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBUNIT, PATHWAY, AND MUTAGENESIS OF LYS-23; TYR-105 AND GLU-142.
RX PubMed=16015285; DOI=10.1038/nature03924;
RA Higgins L.J., Yan F., Liu P., Liu H.W., Drennan C.L.;
RT "Structural insight into antibiotic fosfomycin biosynthesis by a
RT mononuclear iron enzyme.";
RL Nature 437:838-844(2005).
RN [4] {ECO:0007744|PDB:2BNM, ECO:0007744|PDB:2BNN, ECO:0007744|PDB:2BNO}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH ZINC, AND FUNCTION.
RX PubMed=16186494; DOI=10.1073/pnas.0504314102;
RA McLuskey K., Cameron S., Hammerschmidt F., Hunter W.N.;
RT "Structure and reactivity of hydroxypropylphosphonic acid epoxidase in
RT fosfomycin biosynthesis by a cation- and flavin-dependent mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14221-14226(2005).
RN [5] {ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG, ECO:0007744|PDB:3SCH}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH IRON.
RX PubMed=21682308; DOI=10.1021/ja2025728;
RA Yun D., Dey M., Higgins L.J., Yan F., Liu H.W., Drennan C.L.;
RT "Structural basis of regiospecificity of a mononuclear iron enzyme in
RT antibiotic fosfomycin biosynthesis.";
RL J. Am. Chem. Soc. 133:11262-11269(2011).
CC -!- FUNCTION: Non-heme-dependent dioxygenase that catalyzes the oxidative
CC epoxidation of (S)-2-hydroxypropylphosphonate into (1R,2S)-
CC epoxypropylphosphonate, the final step in the biosynthesis of
CC fosfomycin antibiotic. {ECO:0000269|PubMed:16015285,
CC ECO:0000269|PubMed:16186494}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-hydroxypropylphosphonate + H2O2 = (1R,2S)-
CC epoxypropylphosphonate + 2 H2O; Xref=Rhea:RHEA:10808,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:62246,
CC ChEBI:CHEBI:62247; EC=1.11.1.23;
CC Evidence={ECO:0000269|PubMed:16015285};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:16015285};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:16015285};
CC -!- PATHWAY: Antibiotic biosynthesis; fosfomycin biosynthesis.
CC {ECO:0000269|PubMed:16015285, ECO:0000269|PubMed:19516340}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:16015285,
CC ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308}.
CC -!- MISCELLANEOUS: Phosphinothricin tripeptide (PTT) herbicide and
CC fosfomycin antibiotic biosynthesis pathways share early steps starting
CC with phosphoenolpyruvate before the pathways diverge after formation of
CC 2-hydroxyethylphosphonate (HEP). HppE is involved in fosfomycin
CC biosynthesis after divergence of the 2 pathways.
CC {ECO:0000305|PubMed:19516340}.
CC -!- SIMILARITY: Belongs to the non-heme iron-dependent dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; AB016934; BAA32491.1; -; Genomic_DNA.
DR PIR; S60215; S60215.
DR RefSeq; WP_033205181.1; NZ_JNWK01000026.1.
DR PDB; 1ZZ6; X-ray; 2.00 A; A/B=1-198.
DR PDB; 1ZZ7; X-ray; 2.10 A; A/B=1-198.
DR PDB; 1ZZ8; X-ray; 2.30 A; A/B/C=1-198.
DR PDB; 1ZZ9; X-ray; 2.40 A; A/B/C=1-198.
DR PDB; 1ZZB; X-ray; 2.30 A; A/B=1-198.
DR PDB; 1ZZC; X-ray; 1.80 A; A/B=1-198.
DR PDB; 2BNM; X-ray; 1.70 A; A/B=1-198.
DR PDB; 2BNN; X-ray; 2.50 A; A/B=1-198.
DR PDB; 2BNO; X-ray; 1.90 A; A/B=1-198.
DR PDB; 3SCF; X-ray; 2.85 A; A/B/C=1-198.
DR PDB; 3SCG; X-ray; 3.00 A; A/B/C=1-198.
DR PDB; 3SCH; X-ray; 2.10 A; A/B=1-198.
DR PDB; 4J1W; X-ray; 2.72 A; A/B/C=1-198.
DR PDB; 4J1X; X-ray; 2.80 A; A/B/C=2-198.
DR PDBsum; 1ZZ6; -.
DR PDBsum; 1ZZ7; -.
DR PDBsum; 1ZZ8; -.
DR PDBsum; 1ZZ9; -.
DR PDBsum; 1ZZB; -.
DR PDBsum; 1ZZC; -.
DR PDBsum; 2BNM; -.
DR PDBsum; 2BNN; -.
DR PDBsum; 2BNO; -.
DR PDBsum; 3SCF; -.
DR PDBsum; 3SCG; -.
DR PDBsum; 3SCH; -.
DR PDBsum; 4J1W; -.
DR PDBsum; 4J1X; -.
DR AlphaFoldDB; Q56185; -.
DR SMR; Q56185; -.
DR KEGG; ag:BAA32491; -.
DR BioCyc; MetaCyc:MON-13661; -.
DR BRENDA; 1.11.1.23; 6118.
DR BRENDA; 1.14.19.7; 6118.
DR UniPathway; UPA01071; -.
DR EvolutionaryTrace; Q56185; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0016717; F:oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1901766; P:phosphinothricin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR CDD; cd00093; HTH_XRE; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR013096; Cupin_2.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR Pfam; PF07883; Cupin_2; 1.
DR Pfam; PF01381; HTH_3; 1.
DR SMART; SM00530; HTH_XRE; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
DR PROSITE; PS50943; HTH_CROC1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Dioxygenase; DNA-binding; Iron;
KW Metal-binding; NAD; Oxidoreductase.
FT CHAIN 1..198
FT /note="(S)-2-hydroxypropylphosphonic acid epoxidase"
FT /id="PRO_0000422030"
FT DOMAIN 15..70
FT /note="HTH cro/C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT DNA_BIND 26..45
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT BINDING 23
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16186494,
FT ECO:0000269|PubMed:21682308, ECO:0007744|PDB:2BNN,
FT ECO:0007744|PDB:3SCH, ECO:0007744|PDB:4J1W,
FT ECO:0007744|PDB:4J1X"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ8, ECO:0007744|PDB:2BNN,
FT ECO:0007744|PDB:3SCG, ECO:0007744|PDB:3SCH,
FT ECO:0007744|PDB:4J1W, ECO:0007744|PDB:4J1X"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ8, ECO:0007744|PDB:1ZZB,
FT ECO:0007744|PDB:2BNN, ECO:0007744|PDB:3SCF,
FT ECO:0007744|PDB:3SCG, ECO:0007744|PDB:3SCH,
FT ECO:0007744|PDB:4J1W, ECO:0007744|PDB:4J1X"
FT BINDING 135..138
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8,
FT ECO:0007744|PDB:1ZZB, ECO:0007744|PDB:2BNN,
FT ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG,
FT ECO:0007744|PDB:3SCH, ECO:0007744|PDB:4J1W,
FT ECO:0007744|PDB:4J1X"
FT BINDING 138
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8,
FT ECO:0007744|PDB:1ZZ9, ECO:0007744|PDB:2BNM,
FT ECO:0007744|PDB:2BNN, ECO:0007744|PDB:2BNO,
FT ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG,
FT ECO:0007744|PDB:4J1W, ECO:0007744|PDB:4J1X"
FT BINDING 142
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8,
FT ECO:0007744|PDB:1ZZ9, ECO:0007744|PDB:2BNM,
FT ECO:0007744|PDB:2BNN, ECO:0007744|PDB:2BNO,
FT ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG,
FT ECO:0007744|PDB:4J1W, ECO:0007744|PDB:4J1X"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8,
FT ECO:0007744|PDB:1ZZB, ECO:0007744|PDB:2BNN,
FT ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG,
FT ECO:0007744|PDB:3SCH, ECO:0007744|PDB:4J1W"
FT BINDING 180
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16015285,
FT ECO:0000269|PubMed:16186494, ECO:0000269|PubMed:21682308,
FT ECO:0007744|PDB:1ZZ7, ECO:0007744|PDB:1ZZ8,
FT ECO:0007744|PDB:1ZZ9, ECO:0007744|PDB:2BNM,
FT ECO:0007744|PDB:2BNN, ECO:0007744|PDB:2BNO,
FT ECO:0007744|PDB:3SCF, ECO:0007744|PDB:3SCG,
FT ECO:0007744|PDB:4J1W, ECO:0007744|PDB:4J1X"
FT MUTAGEN 23
FT /note="K->A: Abolishes (S)-2-hydroxypropylphosphonic acid
FT epoxidase activity."
FT /evidence="ECO:0000269|PubMed:16015285"
FT MUTAGEN 105
FT /note="Y->F: Abolishes (S)-2-hydroxypropylphosphonic acid
FT epoxidase activity."
FT /evidence="ECO:0000269|PubMed:16015285"
FT MUTAGEN 142
FT /note="E->A: Abolishes (S)-2-hydroxypropylphosphonic acid
FT epoxidase activity."
FT /evidence="ECO:0000269|PubMed:16015285"
FT HELIX 6..21
FT /evidence="ECO:0007829|PDB:2BNM"
FT HELIX 26..33
FT /evidence="ECO:0007829|PDB:2BNM"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:2BNM"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:2BNM"
FT HELIX 53..62
FT /evidence="ECO:0007829|PDB:2BNM"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:1ZZ8"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2BNO"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:2BNM"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:2BNM"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:2BNM"
SQ SEQUENCE 198 AA; 21337 MW; 550D70A1D0D2FC56 CRC64;
MSNTKTASTG FAELLKDRRE QVKMDHAALA SLLGETPETV AAWENGEGGE LTLTQLGRIA
HVLGTSIGAL TPPAGNDLDD GVIIQMPDER PILKGVRDNV DYYVYNCLVR TKRAPSLVPL
VVDVLTDNPD DAKFNSGHAG NEFLFVLEGE IHMKWGDKEN PKEALLPTGA SMFVEEHVPH
AFTAAKGTGS AKLIAVNF
