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Protein

2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase

Gene

menD

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC).UniRule annotation1 Publication

Catalytic activityi

Isochorismate + 2-oxoglutarate = 5-enolpyruvoyl-6-hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2.UniRule annotation1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Mg2+UniRule annotation, Mn2+UniRule annotation
  • thiamine diphosphateUniRule annotationNote: Binds 1 thiamine pyrophosphate per subunit.UniRule annotation

Kineticsi

  1. KM=53 nM for isochorismate (at 22.5 degrees Celsius and pH 7.8)2 Publications
  2. KM=1.5 µM for 2-oxoglutarate (at 22.5 degrees Celsius and pH 7.8)2 Publications
  3. KM=2.4 µM for thiamine diphosphate (at 22.5 degrees Celsius and pH 7.8)2 Publications
  4. KM=80 µM for magnesium ions (at 22.5 degrees Celsius and pH 7.8)2 Publications

    pH dependencei

    Optimum pH is 7-8.2 Publications

    Pathway: 1,4-dihydroxy-2-naphthoate biosynthesis

    This protein is involved in step 2 of the subpathway that synthesizes 1,4-dihydroxy-2-naphthoate from chorismate.UniRule annotation
    Proteins known to be involved in the 7 steps of the subpathway in this organism are:
    1. Isochorismate synthase MenF (menF)
    2. 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase (menD), 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase (menD)
    3. 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (menH), 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (menH)
    4. o-succinylbenzoate synthase (menC), o-succinylbenzoate synthase (menC), o-succinylbenzoate synthase (menE)
    5. 2-succinylbenzoate--CoA ligase (menE)
    6. 1,4-dihydroxy-2-naphthoyl-CoA synthase (menB), 1,4-dihydroxy-2-naphthoyl-CoA synthase (menB)
    7. 1,4-dihydroxy-2-naphthoyl-CoA hydrolase (ydiI), 1,4-dihydroxy-2-naphthoyl-CoA hydrolase (menI)
    This subpathway is part of the pathway 1,4-dihydroxy-2-naphthoate biosynthesis, which is itself part of Quinol/quinone metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes 1,4-dihydroxy-2-naphthoate from chorismate, the pathway 1,4-dihydroxy-2-naphthoate biosynthesis and in Quinol/quinone metabolism.

    Pathway: menaquinone biosynthesis

    This protein is involved in the pathway menaquinone biosynthesis, which is part of Quinol/quinone metabolism.UniRule annotation
    View all proteins of this organism that are known to be involved in the pathway menaquinone biosynthesis and in Quinol/quinone metabolism.

    GO - Molecular functioni

    GO - Biological processi

    • menaquinone biosynthetic process Source: EcoCyc
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Menaquinone biosynthesis

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding, Thiamine pyrophosphate

    Enzyme and pathway databases

    BioCyciEcoCyc:MEND-MONOMER.
    ECOL316407:JW5374-MONOMER.
    MetaCyc:MEND-MONOMER.
    BRENDAi2.2.1.9. 2165.
    SABIO-RKP17109.
    UniPathwayiUPA00079.
    UPA01057; UER00164.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthaseUniRule annotation (EC:2.2.1.9UniRule annotation)
    Short name:
    SEPHCHC synthaseUniRule annotation
    Alternative name(s):
    Menaquinone biosynthesis protein MenDUniRule annotation
    Gene namesi
    Name:menDUniRule annotation
    Ordered Locus Names:b2264, JW5374
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10579. menD.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi55 – 551E → Q: Loss of activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 5565562-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthasePRO_0000090829Add
    BLAST

    Proteomic databases

    PaxDbiP17109.
    PRIDEiP17109.

    Expressioni

    Inductioni

    By isopropyl-beta-D-thiogalactoside (IPTG).1 Publication

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation2 Publications

    Protein-protein interaction databases

    DIPiDIP-10185N.
    IntActiP17109. 1 interaction.
    MINTiMINT-1246688.
    STRINGi511145.b2264.

    Structurei

    Secondary structure

    1
    556
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 1917Combined sources
    Turni20 – 223Combined sources
    Beta strandi25 – 284Combined sources
    Turni32 – 343Combined sources
    Helixi35 – 439Combined sources
    Beta strandi48 – 514Combined sources
    Helixi55 – 6915Combined sources
    Beta strandi73 – 775Combined sources
    Helixi81 – 844Combined sources
    Helixi87 – 9610Combined sources
    Beta strandi100 – 1067Combined sources
    Helixi109 – 1113Combined sources
    Beta strandi112 – 1154Combined sources
    Turni123 – 1286Combined sources
    Beta strandi130 – 1356Combined sources
    Helixi145 – 15713Combined sources
    Beta strandi164 – 1696Combined sources
    Helixi183 – 1875Combined sources
    Helixi188 – 1947Combined sources
    Beta strandi199 – 2013Combined sources
    Beta strandi205 – 2073Combined sources
    Helixi214 – 2174Combined sources
    Beta strandi222 – 2265Combined sources
    Helixi231 – 24414Combined sources
    Beta strandi248 – 2503Combined sources
    Turni252 – 2543Combined sources
    Helixi263 – 2664Combined sources
    Helixi270 – 2767Combined sources
    Beta strandi280 – 2878Combined sources
    Helixi292 – 3009Combined sources
    Beta strandi304 – 3129Combined sources
    Beta strandi322 – 3287Combined sources
    Helixi330 – 3367Combined sources
    Helixi349 – 36113Combined sources
    Turni362 – 3654Combined sources
    Beta strandi366 – 3683Combined sources
    Helixi369 – 3746Combined sources
    Helixi376 – 3783Combined sources
    Beta strandi385 – 3884Combined sources
    Helixi392 – 4009Combined sources
    Beta strandi409 – 4113Combined sources
    Beta strandi418 – 4203Combined sources
    Helixi421 – 43212Combined sources
    Beta strandi436 – 4416Combined sources
    Helixi442 – 4476Combined sources
    Helixi449 – 4513Combined sources
    Helixi452 – 4554Combined sources
    Beta strandi462 – 4698Combined sources
    Helixi474 – 4774Combined sources
    Helixi482 – 4887Combined sources
    Helixi498 – 5036Combined sources
    Beta strandi507 – 5093Combined sources
    Helixi514 – 52411Combined sources
    Beta strandi527 – 53610Combined sources
    Helixi541 – 55414Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JLAX-ray2.81A/B/C/D1-556[»]
    2JLCX-ray2.50A/B1-556[»]
    3FLMX-ray2.70A/B1-556[»]
    3HWWX-ray1.95A/D1-556[»]
    3HWXX-ray2.601/A/B/I/J/R/S/Z1-556[»]
    ProteinModelPortaliP17109.
    SMRiP17109. Positions 1-556.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP17109.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the TPP enzyme family. MenD subfamily.UniRule annotationCurated

    Phylogenomic databases

    eggNOGiCOG1165.
    HOGENOMiHOG000218360.
    InParanoidiP17109.
    KOiK02551.
    OMAiQKPWLLE.
    OrthoDBiEOG6NWBQW.
    PhylomeDBiP17109.

    Family and domain databases

    Gene3Di3.40.50.970. 2 hits.
    HAMAPiMF_01659. MenD.
    InterProiIPR004433. MenaQ_synth_MenD.
    IPR029061. THDP-binding.
    IPR012001. Thiamin_PyroP_enz_TPP-bd_dom.
    IPR011766. TPP_enzyme-bd_C.
    [Graphical view]
    PfamiPF02775. TPP_enzyme_C. 1 hit.
    PF02776. TPP_enzyme_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF004983. MenD. 1 hit.
    SUPFAMiSSF52518. SSF52518. 2 hits.
    TIGRFAMsiTIGR00173. menD. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P17109-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSVSAFNRRW AAVILEALTR HGVRHICIAP GSRSTPLTLA AAENSAFIHH
    60 70 80 90 100
    THFDERGLGH LALGLAKVSK QPVAVIVTSG TAVANLYPAL IEAGLTGEKL
    110 120 130 140 150
    ILLTADRPPE LIDCGANQAI RQPGMFASHP THSISLPRPT QDIPARWLVS
    160 170 180 190 200
    TIDHALGTLH AGGVHINCPF AEPLYGEMDD TGLSWQQRLG DWWQDDKPWL
    210 220 230 240 250
    REAPRLESEK QRDWFFWRQK RGVVVAGRMS AEEGKKVALW AQTLGWPLIG
    260 270 280 290 300
    DVLSQTGQPL PCADLWLGNA KATSELQQAQ IVVQLGSSLT GKRLLQWQAS
    310 320 330 340 350
    CEPEEYWIVD DIEGRLDPAH HRGRRLIANI ADWLELHPAE KRQPWCVEIP
    360 370 380 390 400
    RLAEQAMQAV IARRDAFGEA QLAHRICDYL PEQGQLFVGN SLVVRLIDAL
    410 420 430 440 450
    SQLPAGYPVY SNRGASGIDG LLSTAAGVQR ASGKPTLAIV GDLSALYDLN
    460 470 480 490 500
    ALALLRQVSA PLVLIVVNNN GGQIFSLLPT PQSERERFYL MPQNVHFEHA
    510 520 530 540 550
    AAMFELKYHR PQNWQELETA FADAWRTPTT TVIEMVVNDT DGAQTLQQLL

    AQVSHL
    Length:556
    Mass (Da):61,367
    Last modified:November 1, 1997 - v4
    Checksum:i278201D02243E76D
    GO

    Sequence cautioni

    The sequence AAA24153.1 differs from that shown. Reason: Frameshift at position 370. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti42 – 421Missing in AAA24153 (PubMed:2666397).Curated
    Sequence conflicti163 – 18321GVHIN…DDTGL → ESISTARLLNRCMAKWTIPG F in AAA24153 (PubMed:2666397).CuratedAdd
    BLAST
    Sequence conflicti398 – 3981Missing in AAA24153 (PubMed:2666397).Curated
    Sequence conflicti543 – 55614AQTLQ…QVSHL → RKRSSNFWRR in AAB59060 (Ref. 6) CuratedAdd
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U54790 Genomic DNA. Translation: AAC44304.1.
    U00096 Genomic DNA. Translation: AAC75324.1.
    AP009048 Genomic DNA. Translation: BAA16089.2.
    M21787 Genomic DNA. Translation: AAA24153.1. Frameshift.
    L04464 Genomic DNA. Translation: AAB59060.1.
    L35030 Genomic DNA. Translation: AAA24150.1.
    PIRiF64997.
    RefSeqiNP_416767.1. NC_000913.3.

    Genome annotation databases

    EnsemblBacteriaiAAC75324; AAC75324; b2264.
    BAA16089; BAA16089; BAA16089.
    GeneIDi946720.
    KEGGiecj:Y75_p2228.
    eco:b2264.
    PATRICi32119895. VBIEscCol129921_2357.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U54790 Genomic DNA. Translation: AAC44304.1.
    U00096 Genomic DNA. Translation: AAC75324.1.
    AP009048 Genomic DNA. Translation: BAA16089.2.
    M21787 Genomic DNA. Translation: AAA24153.1. Frameshift.
    L04464 Genomic DNA. Translation: AAB59060.1.
    L35030 Genomic DNA. Translation: AAA24150.1.
    PIRiF64997.
    RefSeqiNP_416767.1. NC_000913.3.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JLAX-ray2.81A/B/C/D1-556[»]
    2JLCX-ray2.50A/B1-556[»]
    3FLMX-ray2.70A/B1-556[»]
    3HWWX-ray1.95A/D1-556[»]
    3HWXX-ray2.601/A/B/I/J/R/S/Z1-556[»]
    ProteinModelPortaliP17109.
    SMRiP17109. Positions 1-556.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-10185N.
    IntActiP17109. 1 interaction.
    MINTiMINT-1246688.
    STRINGi511145.b2264.

    Proteomic databases

    PaxDbiP17109.
    PRIDEiP17109.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC75324; AAC75324; b2264.
    BAA16089; BAA16089; BAA16089.
    GeneIDi946720.
    KEGGiecj:Y75_p2228.
    eco:b2264.
    PATRICi32119895. VBIEscCol129921_2357.

    Organism-specific databases

    EchoBASEiEB0574.
    EcoGeneiEG10579. menD.

    Phylogenomic databases

    eggNOGiCOG1165.
    HOGENOMiHOG000218360.
    InParanoidiP17109.
    KOiK02551.
    OMAiQKPWLLE.
    OrthoDBiEOG6NWBQW.
    PhylomeDBiP17109.

    Enzyme and pathway databases

    UniPathwayiUPA00079.
    UPA01057; UER00164.
    BioCyciEcoCyc:MEND-MONOMER.
    ECOL316407:JW5374-MONOMER.
    MetaCyc:MEND-MONOMER.
    BRENDAi2.2.1.9. 2165.
    SABIO-RKP17109.

    Miscellaneous databases

    EvolutionaryTraceiP17109.
    PROiP17109.

    Family and domain databases

    Gene3Di3.40.50.970. 2 hits.
    HAMAPiMF_01659. MenD.
    InterProiIPR004433. MenaQ_synth_MenD.
    IPR029061. THDP-binding.
    IPR012001. Thiamin_PyroP_enz_TPP-bd_dom.
    IPR011766. TPP_enzyme-bd_C.
    [Graphical view]
    PfamiPF02775. TPP_enzyme_C. 1 hit.
    PF02776. TPP_enzyme_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF004983. MenD. 1 hit.
    SUPFAMiSSF52518. SSF52518. 2 hits.
    TIGRFAMsiTIGR00173. menD. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A new isochorismate synthase specifically involved in menaquinone (vitamin K2) biosynthesis encoded by the menF gene."
      Daruwala R., Kwon O., Meganathan R., Hudspeth M.E.S.
      FEMS Microbiol. Lett. 140:159-163(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features."
      Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T., Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K., Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T.
      , Oyama S., Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H., Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.
      DNA Res. 4:91-113(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    5. "Sequence and overexpression of the menD gene from Escherichia coli."
      Popp J.L.
      J. Bacteriol. 171:4349-4354(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-507.
    6. Sharma V., Hudspeth M.E., Meganathan R.
      Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 536-556.
      Strain: K12.
    7. "Menaquinone (vitamin K2) biosynthesis: evidence that the Escherichia coli menD gene encodes both 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid synthase and alpha-ketoglutarate decarboxylase activities."
      Palaniappan C., Sharma V., Hudspeth M.E., Meganathan R.
      J. Bacteriol. 174:8111-8118(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, PRELIMINARY FUNCTION.
      Strain: K12.
    8. "Steady-state kinetics and molecular evolution of Escherichia coli MenD [(1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase], an anomalous thiamin diphosphate-dependent decarboxylase-carboligase."
      Bhasin M., Billinsky J.L., Palmer D.R.J.
      Biochemistry 42:13496-13504(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, COFACTOR, MUTAGENESIS OF GLU-55, BIOPHYSICOCHEMICAL PROPERTIES.
    9. "Crystallization and preliminary X-ray analysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase (MenD) from Escherichia coli."
      Sieminska E.A.L., Macova A., Palmer D.R.J., Sanders D.A.R.
      Acta Crystallogr. F 61:489-492(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CRYSTALLIZATION, COFACTOR, SUBUNIT.
    10. "Menaquinone biosynthesis in Escherichia coli: identification of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate as a novel intermediate and re-evaluation of MenD activity."
      Jiang M., Cao Y., Guo Z.-F., Chen M., Chen X., Guo Z.
      Biochemistry 46:10979-10989(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A SEPHCHC SYNTHASE, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.

    Entry informationi

    Entry nameiMEND_ECOLI
    AccessioniPrimary (citable) accession number: P17109
    Secondary accession number(s): P76478, P78180, P78181
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: November 1, 1997
    Last modified: June 24, 2015
    This is version 139 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    Was originally thought (PubMed:1459959, PubMed:14621995 and PubMed:16511076) to be a 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase but further protein analysis clearly suggests that it is a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) synthase.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.