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Protein

2-hydroxyethylphosphonate dioxygenase

Gene

hepD

Organism
Streptomyces viridochromogenes (strain DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-heme-dependent dioxygenase that catalyzes the conversion of 2-hydroxyethylphosphonate (HEP) to hydroxymethylphosphonate (HMP) in the biosynthesis of phosphinothricin tripeptide (PTT). PTT contains the unusual amino acid phosphinothricin attached to 2 alanine residues. Synthetic phosphinothricin (glufosinate) is a key component of commercial herbicides.5 Publications

Catalytic activityi

2-hydroxyethylphosphonate + O2 = hydroxymethylphosphonate + formate.4 Publications

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Kineticsi

kcat is 0.35 sec(-1).

  1. KM=9.8 µM for 2-hydroxyethylphosphonate1 Publication
  2. KM=33 µM for O21 Publication

    Pathwayi: phosphonate biosynthesis

    This protein is involved in the pathway phosphonate biosynthesis, which is part of Phosphorus metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway phosphonate biosynthesis and in Phosphorus metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei16 – 161Substrate; shared with dimeric partnerCombined sources
    Binding sitei98 – 981SubstrateCombined sources
    Binding sitei126 – 1261SubstrateCombined sources
    Metal bindingi129 – 1291Iron; via tele nitrogenCombined sources2 Publications
    Binding sitei176 – 1761SubstrateCombined sources
    Metal bindingi182 – 1821Iron; via tele nitrogenCombined sources2 Publications
    Binding sitei182 – 1821SubstrateCombined sources
    Binding sitei196 – 1961SubstrateCombined sources

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi19 – 3820H-T-H motifBy similarityAdd
    BLAST
    DNA bindingi245 – 26521H-T-H motifBy similarityAdd
    BLAST

    GO - Molecular functioni

    GO - Biological processi

    • organic phosphonate biosynthetic process Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • phosphinothricin biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    DNA-binding, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15041.
    BRENDAi1.13.11.72. 6116.
    UniPathwayiUPA00960.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2-hydroxyethylphosphonate dioxygenase (EC:1.13.11.724 Publications)
    Alternative name(s):
    Hydroxyethylphosphonate dioxygenase
    Phosphinothricin tripeptide biosynthesis protein D
    Gene namesi
    Name:hepD
    Synonyms:phpD
    ORF Names:SSQG_01041
    OrganismiStreptomyces viridochromogenes (strain DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494)
    Taxonomic identifieri591159 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces
    Proteomesi
    • UP000004184 Componenti: Unassembled WGS sequence

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi16 – 161K → A: Abolishes 2-hydroxyethylphosphonate dioxygenase activity. 1 Publication
    Mutagenesisi90 – 901R → A: Results in a much higher apparent KM for 2-hydroxyethylphosphonate. Caanot be saturated in (O2). 1 Publication
    Mutagenesisi98 – 981Y → F: Still able to convert 2-hydroxyethylphosphonate to hydroxymethylphosphonate and formate; however, in contrast to wild-type enzyme which consumes O(2) without a loss of catalytic activity, the rate of consumption of O(2) gradually decreases until the enzyme has lost all activity well before substrate has been consumed. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 4434432-hydroxyethylphosphonate dioxygenasePRO_0000422032Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    DIPiDIP-59765N.
    STRINGi591159.SSQG_01041.

    Structurei

    Secondary structure

    1
    443
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi5 – 1511Combined sources
    Helixi19 – 268Combined sources
    Helixi30 – 367Combined sources
    Beta strandi37 – 393Combined sources
    Turni43 – 464Combined sources
    Helixi49 – 557Combined sources
    Helixi60 – 623Combined sources
    Beta strandi73 – 764Combined sources
    Helixi78 – 825Combined sources
    Beta strandi86 – 905Combined sources
    Beta strandi93 – 1008Combined sources
    Beta strandi111 – 1155Combined sources
    Beta strandi133 – 1419Combined sources
    Beta strandi143 – 1464Combined sources
    Beta strandi148 – 1503Combined sources
    Turni153 – 1553Combined sources
    Beta strandi156 – 1594Combined sources
    Beta strandi173 – 1764Combined sources
    Beta strandi183 – 1908Combined sources
    Beta strandi192 – 1987Combined sources
    Helixi204 – 2107Combined sources
    Helixi215 – 22410Combined sources
    Helixi231 – 24111Combined sources
    Helixi246 – 2538Combined sources
    Helixi257 – 2659Combined sources
    Helixi270 – 28314Combined sources
    Helixi287 – 2904Combined sources
    Beta strandi298 – 3003Combined sources
    Turni301 – 3033Combined sources
    Helixi307 – 3126Combined sources
    Beta strandi315 – 3173Combined sources
    Beta strandi320 – 3245Combined sources
    Beta strandi335 – 34511Combined sources
    Beta strandi353 – 36311Combined sources
    Beta strandi365 – 3717Combined sources
    Beta strandi374 – 3807Combined sources
    Beta strandi385 – 3884Combined sources
    Beta strandi394 – 40714Combined sources
    Helixi413 – 4208Combined sources
    Beta strandi422 – 4243Combined sources
    Helixi425 – 4306Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3G7DX-ray1.80A1-443[»]
    3GBFX-ray1.92A1-443[»]
    3RZZX-ray2.20A1-443[»]
    4YARX-ray1.75A1-443[»]
    ProteinModelPortaliQ5IW40.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ5IW40.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini8 – 6356HTH cro/C1-type 1Add
    BLAST
    Domaini234 – 29057HTH cro/C1-type 2Add
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    KOiK12905.

    Family and domain databases

    Gene3Di1.10.260.40. 1 hit.
    InterProiIPR001387. Cro/C1-type_HTH.
    IPR010982. Lambda_DNA-bd_dom.
    IPR011051. RmlC_Cupin.
    [Graphical view]
    SMARTiSM00530. HTH_XRE. 2 hits.
    [Graphical view]
    SUPFAMiSSF51182. SSF51182. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q5IW40-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MRIDPFKLAH WMNARKYTAA QTADLAGLPL DDLRRLLGDE ANEPDPAAAT
    60 70 80 90 100
    ALAEALSVEP SQLAADAHRN LTVVHKSAEE MHASRRPIQR DGIHFYNYYT
    110 120 130 140 150
    LAAPEGRVAP VVLDILCPSD RLPALNNGHL EPAITVNLGP GDINGRWGEE
    160 170 180 190 200
    ITPQTWRVLH ANHGGDRWIT GDSYVEPSYC PHSYSLAGDA PARIVSYTAQ
    210 220 230 240 250
    SNISPLMTEA NNWSTGAFEE ALKALSGKVS AGSVLDLFLA RRAHTRTSAA
    260 270 280 290 300
    EAAGVPPADL EAALRSPASE TGLTVLRTLG RALGFDYRVL LPADDQHDGV
    310 320 330 340 350
    GKTWTTIEDS RRSRRTFGTY EAASMASAAH LPDLVGSFLR VDADGRGADL
    360 370 380 390 400
    IDHAENHYVV TEGRLTLEWD GPDGPASVEL EPDGSAWTGP FVRHRWHGTG
    410 420 430 440
    TVLKFGSGAH LGYQDWLELT NTFEPAATLR RGRRDLAGWG YDN
    Length:443
    Mass (Da):48,091
    Last modified:December 4, 2007 - v2
    Checksum:i5ADBA86C73E65B48
    GO

    Sequence cautioni

    The sequence CAJ14042.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X65195 Genomic DNA. Translation: CAJ14042.1. Different initiation.
    AY632421 Genomic DNA. Translation: AAU00079.2.
    GG657757 Genomic DNA. Translation: EFL30523.1.
    RefSeqiWP_003988638.1. NZ_GG657757.1.

    Genome annotation databases

    EnsemblBacteriaiEFL30523; EFL30523; SSQG_01041.
    KEGGiag:AAU00079.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X65195 Genomic DNA. Translation: CAJ14042.1. Different initiation.
    AY632421 Genomic DNA. Translation: AAU00079.2.
    GG657757 Genomic DNA. Translation: EFL30523.1.
    RefSeqiWP_003988638.1. NZ_GG657757.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3G7DX-ray1.80A1-443[»]
    3GBFX-ray1.92A1-443[»]
    3RZZX-ray2.20A1-443[»]
    4YARX-ray1.75A1-443[»]
    ProteinModelPortaliQ5IW40.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-59765N.
    STRINGi591159.SSQG_01041.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiEFL30523; EFL30523; SSQG_01041.
    KEGGiag:AAU00079.

    Phylogenomic databases

    KOiK12905.

    Enzyme and pathway databases

    UniPathwayiUPA00960.
    BioCyciMetaCyc:MONOMER-15041.
    BRENDAi1.13.11.72. 6116.

    Miscellaneous databases

    EvolutionaryTraceiQ5IW40.

    Family and domain databases

    Gene3Di1.10.260.40. 1 hit.
    InterProiIPR001387. Cro/C1-type_HTH.
    IPR010982. Lambda_DNA-bd_dom.
    IPR011051. RmlC_Cupin.
    [Graphical view]
    SMARTiSM00530. HTH_XRE. 2 hits.
    [Graphical view]
    SUPFAMiSSF51182. SSF51182. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The peptide synthetase gene phsA from Streptomyces viridochromogenes is not juxtaposed with other genes involved in nonribosomal biosynthesis of peptides."
      Schwartz D., Alijah R., Nussbaumer B., Pelzer S., Wohlleben W.
      Appl. Environ. Microbiol. 62:570-577(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494.
    2. "Molecular cloning, sequence analysis, and heterologous expression of the phosphinothricin tripeptide biosynthetic gene cluster from Streptomyces viridochromogenes DSM 40736."
      Blodgett J.A., Zhang J.K., Metcalf W.W.
      Antimicrob. Agents Chemother. 49:230-240(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494.
    3. "Annotation of Streptomyces viridochromogenes strain DSM 40736."
      The Broad Institute Genome Sequencing Platform, Broad Institute Microbial Sequencing Center
      Fischbach M., Godfrey P., Ward D., Young S., Zeng Q., Koehrsen M., Alvarado L., Berlin A.M., Bochicchio J., Borenstein D., Chapman S.B., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J., Griggs A., Gujja S.
      , Heilman E.R., Heiman D.I., Hepburn T.A., Howarth C., Jen D., Larson L., Lewis B., Mehta T., Park D., Pearson M., Richards J., Roberts A., Saif S., Shea T.D., Shenoy N., Sisk P., Stolte C., Sykes S.N., Thomson T., Walk T., White J., Yandava C., Straight P., Clardy J., Hung D., Kolter R., Mekalanos J., Walker S., Walsh C.T., Wieland-Brown L.C., Haas B., Nusbaum C., Birren B.
      Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494.
    4. "Unusual transformations in the biosynthesis of the antibiotic phosphinothricin tripeptide."
      Blodgett J.A., Thomas P.M., Li G., Velasquez J.E., van der Donk W.A., Kelleher N.L., Metcalf W.W.
      Nat. Chem. Biol. 3:480-485(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494.
    5. "Hydroperoxylation by hydroxyethylphosphonate dioxygenase."
      Whitteck J.T., Cicchillo R.M., van der Donk W.A.
      J. Am. Chem. Soc. 131:16225-16232(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM.
    6. Cited for: FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM.
    7. "An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis."
      Cicchillo R.M., Zhang H., Blodgett J.A., Whitteck J.T., Li G., Nair S.K., van der Donk W.A., Metcalf W.W.
      Nature 459:871-874(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COBALT, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY.
    8. "Mechanism and substrate recognition of 2-hydroxyethylphosphonate dioxygenase."
      Peck S.C., Cooke H.A., Cicchillo R.M., Malova P., Hammerschmidt F., Nair S.K., van der Donk W.A.
      Biochemistry 50:6598-6605(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH COBALT AND 2-HYDROXYETHYLPHOSPHONATE, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-16; ARG-90 AND TYR-98.

    Entry informationi

    Entry nameiHEPD_STRVT
    AccessioniPrimary (citable) accession number: Q5IW40
    Secondary accession number(s): D9XF44, Q4JFE9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 3, 2013
    Last sequence update: December 4, 2007
    Last modified: April 13, 2016
    This is version 58 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Mediates the cleavage of the carbon-carbon bond of 2-hydroxyethylphosphonate (HEP) to produce hydroxymethylphosphonate (HMP) and formate without input of electrons or use of any organic cofactors. Reaction was initially supposed to follow a Criegee rearrangement with a phosphorus-based migrating group (PubMed:19839620). However, it was laster shown that it is not the case (PubMed:21381767).2 Publications
    Phosphinothricin tripeptide (PTT) herbicide and fosfomycin antibiotic biosynthesis pathways share early steps starting with phosphoenolpyruvate before the pathways diverge after formation of 2-hydroxyethylphosphonate (HEP) (PubMed:17632514). HepD is involved in phosphinothricin tripeptide (PTT) herbicide biosynthesis after divergence of the 2 pathways (PubMed:19516340).2 Publications

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.