HEPD_STRVT
ID HEPD_STRVT Reviewed; 443 AA.
AC Q5IW40; D9XF44; Q4JFE9;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=2-hydroxyethylphosphonate dioxygenase;
DE EC=1.13.11.72 {ECO:0000269|PubMed:19516340, ECO:0000269|PubMed:19839620, ECO:0000269|PubMed:21381767, ECO:0000269|PubMed:21711001};
DE AltName: Full=Hydroxyethylphosphonate dioxygenase;
DE AltName: Full=Phosphinothricin tripeptide biosynthesis protein D;
GN Name=hepD; Synonyms=phpD; ORFNames=SSQG_01041;
OS Streptomyces viridochromogenes (strain DSM 40736 / JCM 4977 / BCRC 1201 /
OS Tue 494).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=591159;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494;
RX PubMed=8593056; DOI=10.1128/aem.62.2.570-577.1996;
RA Schwartz D., Alijah R., Nussbaumer B., Pelzer S., Wohlleben W.;
RT "The peptide synthetase gene phsA from Streptomyces viridochromogenes is
RT not juxtaposed with other genes involved in nonribosomal biosynthesis of
RT peptides.";
RL Appl. Environ. Microbiol. 62:570-577(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494;
RX PubMed=15616300; DOI=10.1128/aac.49.1.230-240.2005;
RA Blodgett J.A., Zhang J.K., Metcalf W.W.;
RT "Molecular cloning, sequence analysis, and heterologous expression of the
RT phosphinothricin tripeptide biosynthetic gene cluster from Streptomyces
RT viridochromogenes DSM 40736.";
RL Antimicrob. Agents Chemother. 49:230-240(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494;
RG The Broad Institute Genome Sequencing Platform;
RG Broad Institute Microbial Sequencing Center;
RA Fischbach M., Godfrey P., Ward D., Young S., Zeng Q., Koehrsen M.,
RA Alvarado L., Berlin A.M., Bochicchio J., Borenstein D., Chapman S.B.,
RA Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J., Griggs A.,
RA Gujja S., Heilman E.R., Heiman D.I., Hepburn T.A., Howarth C., Jen D.,
RA Larson L., Lewis B., Mehta T., Park D., Pearson M., Richards J.,
RA Roberts A., Saif S., Shea T.D., Shenoy N., Sisk P., Stolte C., Sykes S.N.,
RA Thomson T., Walk T., White J., Yandava C., Straight P., Clardy J., Hung D.,
RA Kolter R., Mekalanos J., Walker S., Walsh C.T., Wieland-Brown L.C.,
RA Haas B., Nusbaum C., Birren B.;
RT "Annotation of Streptomyces viridochromogenes strain DSM 40736.";
RL Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RC STRAIN=DSM 40736 / JCM 4977 / BCRC 1201 / Tue 494;
RX PubMed=17632514; DOI=10.1038/nchembio.2007.9;
RA Blodgett J.A., Thomas P.M., Li G., Velasquez J.E., van der Donk W.A.,
RA Kelleher N.L., Metcalf W.W.;
RT "Unusual transformations in the biosynthesis of the antibiotic
RT phosphinothricin tripeptide.";
RL Nat. Chem. Biol. 3:480-485(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND REACTION MECHANISM.
RX PubMed=19839620; DOI=10.1021/ja906238r;
RA Whitteck J.T., Cicchillo R.M., van der Donk W.A.;
RT "Hydroperoxylation by hydroxyethylphosphonate dioxygenase.";
RL J. Am. Chem. Soc. 131:16225-16232(2009).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND REACTION MECHANISM.
RX PubMed=21381767; DOI=10.1021/ja1113326;
RA Whitteck J.T., Malova P., Peck S.C., Cicchillo R.M., Hammerschmidt F.,
RA van der Donk W.A.;
RT "On the stereochemistry of 2-hydroxyethylphosphonate dioxygenase.";
RL J. Am. Chem. Soc. 133:4236-4239(2011).
RN [7] {ECO:0007744|PDB:3G7D}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COBALT, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, 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 [8] {ECO:0007744|PDB:3RZZ}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH COBALT AND
RP 2-HYDROXYETHYLPHOSPHONATE, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF LYS-16; ARG-90 AND
RP TYR-98.
RX PubMed=21711001; DOI=10.1021/bi200804r;
RA Peck S.C., Cooke H.A., Cicchillo R.M., Malova P., Hammerschmidt F.,
RA Nair S.K., van der Donk W.A.;
RT "Mechanism and substrate recognition of 2-hydroxyethylphosphonate
RT dioxygenase.";
RL Biochemistry 50:6598-6605(2011).
CC -!- FUNCTION: Non-heme-dependent dioxygenase that catalyzes the conversion
CC of 2-hydroxyethylphosphonate (HEP) to hydroxymethylphosphonate (HMP) in
CC the biosynthesis of phosphinothricin tripeptide (PTT). PTT contains the
CC unusual amino acid phosphinothricin attached to 2 alanine residues.
CC Synthetic phosphinothricin (glufosinate) is a key component of
CC commercial herbicides. {ECO:0000269|PubMed:17632514,
CC ECO:0000269|PubMed:19516340, ECO:0000269|PubMed:19839620,
CC ECO:0000269|PubMed:21381767, ECO:0000269|PubMed:21711001}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyethylphosphonate + O2 = formate + H(+) +
CC hydroxymethylphosphonate; Xref=Rhea:RHEA:34791, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:60991,
CC ChEBI:CHEBI:71199; EC=1.13.11.72;
CC Evidence={ECO:0000269|PubMed:19516340, ECO:0000269|PubMed:19839620,
CC ECO:0000269|PubMed:21381767, ECO:0000269|PubMed:21711001};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:19516340};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19516340};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.8 uM for 2-hydroxyethylphosphonate
CC {ECO:0000269|PubMed:21711001};
CC KM=33 uM for O(2) {ECO:0000269|PubMed:21711001};
CC Note=kcat is 0.35 sec(-1).;
CC -!- PATHWAY: Phosphorus metabolism; phosphonate biosynthesis.
CC {ECO:0000269|PubMed:19516340}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19516340,
CC ECO:0000269|PubMed:21711001}.
CC -!- INTERACTION:
CC Q5IW40; Q5IW40: hepD; NbExp=2; IntAct=EBI-15787755, EBI-15787755;
CC -!- MISCELLANEOUS: Mediates the cleavage of the carbon-carbon bond of 2-
CC hydroxyethylphosphonate (HEP) to produce hydroxymethylphosphonate (HMP)
CC and formate without input of electrons or use of any organic cofactors.
CC Reaction was initially supposed to follow a Criegee rearrangement with
CC a phosphorus-based migrating group (PubMed:19839620). However, it was
CC laster shown that it is not the case (PubMed:21381767).
CC {ECO:0000305|PubMed:19839620, ECO:0000305|PubMed:21381767}.
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) (PubMed:17632514). HepD is involved in
CC phosphinothricin tripeptide (PTT) herbicide biosynthesis after
CC divergence of the 2 pathways (PubMed:19516340).
CC {ECO:0000305|PubMed:17632514, ECO:0000305|PubMed:19516340}.
CC -!- SIMILARITY: Belongs to the non-heme iron-dependent dioxygenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAJ14042.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X65195; CAJ14042.1; ALT_INIT; Genomic_DNA.
DR EMBL; AY632421; AAU00079.2; -; Genomic_DNA.
DR EMBL; GG657757; EFL30523.1; -; Genomic_DNA.
DR RefSeq; WP_003988638.1; NZ_GG657757.1.
DR PDB; 3G7D; X-ray; 1.80 A; A=1-443.
DR PDB; 3GBF; X-ray; 1.92 A; A=1-443.
DR PDB; 3RZZ; X-ray; 2.20 A; A=1-443.
DR PDB; 4YAR; X-ray; 1.75 A; A=1-443.
DR PDBsum; 3G7D; -.
DR PDBsum; 3GBF; -.
DR PDBsum; 3RZZ; -.
DR PDBsum; 4YAR; -.
DR AlphaFoldDB; Q5IW40; -.
DR SMR; Q5IW40; -.
DR DIP; DIP-59765N; -.
DR STRING; 591159.ACEZ01000045_gene2950; -.
DR EnsemblBacteria; EFL30523; EFL30523; SSQG_01041.
DR KEGG; ag:AAU00079; -.
DR eggNOG; ENOG5031FT4; Bacteria.
DR HOGENOM; CLU_622432_0_0_11; -.
DR OrthoDB; 603921at2; -.
DR BioCyc; MetaCyc:MON-15041; -.
DR BRENDA; 1.13.11.72; 6116.
DR UniPathway; UPA00960; -.
DR EvolutionaryTrace; Q5IW40; -.
DR Proteomes; UP000004184; Unassembled WGS sequence.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0032923; P:organic phosphonate biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901766; P:phosphinothricin biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.260.40; -; 1.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR SMART; SM00530; HTH_XRE; 2.
DR SUPFAM; SSF51182; SSF51182; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; DNA-binding; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..443
FT /note="2-hydroxyethylphosphonate dioxygenase"
FT /id="PRO_0000422032"
FT DOMAIN 8..63
FT /note="HTH cro/C1-type 1"
FT DOMAIN 234..290
FT /note="HTH cro/C1-type 2"
FT DNA_BIND 19..38
FT /note="H-T-H motif"
FT /evidence="ECO:0000250"
FT DNA_BIND 245..265
FT /note="H-T-H motif"
FT /evidence="ECO:0000250"
FT BINDING 16
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0007744|PDB:3GBF"
FT BINDING 98
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:3GBF"
FT BINDING 126
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:3GBF"
FT BINDING 129
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:19516340,
FT ECO:0000269|PubMed:21711001, ECO:0007744|PDB:3G7D,
FT ECO:0007744|PDB:3GBF, ECO:0007744|PDB:3RZZ"
FT BINDING 176
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:3GBF"
FT BINDING 182
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:19516340,
FT ECO:0000269|PubMed:21711001, ECO:0007744|PDB:3G7D,
FT ECO:0007744|PDB:3GBF, ECO:0007744|PDB:3RZZ"
FT BINDING 182
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:3GBF"
FT BINDING 196
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:3GBF"
FT MUTAGEN 16
FT /note="K->A: Abolishes 2-hydroxyethylphosphonate
FT dioxygenase activity."
FT /evidence="ECO:0000269|PubMed:21711001"
FT MUTAGEN 90
FT /note="R->A: Results in a much higher apparent KM for 2-
FT hydroxyethylphosphonate. Caanot be saturated in (O2)."
FT /evidence="ECO:0000269|PubMed:21711001"
FT MUTAGEN 98
FT /note="Y->F: Still able to convert 2-
FT hydroxyethylphosphonate to hydroxymethylphosphonate and
FT formate; however, in contrast to wild-type enzyme which
FT consumes O(2) without a loss of catalytic activity, the
FT rate of consumption of O(2) gradually decreases until the
FT enzyme has lost all activity well before substrate has been
FT consumed."
FT /evidence="ECO:0000269|PubMed:21711001"
FT HELIX 5..15
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 19..26
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 30..36
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:4YAR"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 49..55
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 78..82
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 133..141
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:4YAR"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 192..198
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 204..210
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 231..241
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 257..265
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 270..283
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:3RZZ"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 307..312
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 353..363
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 374..380
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 394..407
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 413..420
FT /evidence="ECO:0007829|PDB:4YAR"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:4YAR"
FT HELIX 425..430
FT /evidence="ECO:0007829|PDB:4YAR"
SQ SEQUENCE 443 AA; 48091 MW; 5ADBA86C73E65B48 CRC64;
MRIDPFKLAH WMNARKYTAA QTADLAGLPL DDLRRLLGDE ANEPDPAAAT ALAEALSVEP
SQLAADAHRN LTVVHKSAEE MHASRRPIQR DGIHFYNYYT LAAPEGRVAP VVLDILCPSD
RLPALNNGHL EPAITVNLGP GDINGRWGEE ITPQTWRVLH ANHGGDRWIT GDSYVEPSYC
PHSYSLAGDA PARIVSYTAQ SNISPLMTEA NNWSTGAFEE ALKALSGKVS AGSVLDLFLA
RRAHTRTSAA EAAGVPPADL EAALRSPASE TGLTVLRTLG RALGFDYRVL LPADDQHDGV
GKTWTTIEDS RRSRRTFGTY EAASMASAAH LPDLVGSFLR VDADGRGADL IDHAENHYVV
TEGRLTLEWD GPDGPASVEL EPDGSAWTGP FVRHRWHGTG TVLKFGSGAH LGYQDWLELT
NTFEPAATLR RGRRDLAGWG YDN
