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Protein

KHG/KDPG aldolase

Gene

eda

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

Functioni

Involved in the degradation of glucose via the Entner-Doudoroff pathway. Catalyzes the reversible, stereospecific retro-aldol cleavage of 2-Keto-3-deoxy-6-phosphogluconate (KDPG) to pyruvate and D-glyceraldehyde-3-phosphate. In the synthetic direction, it catalyzes the addition of pyruvate to electrophilic aldehydes with si-facial selectivity. It accepts some nucleophiles other than pyruvate, including 2-oxobutanoate, phenylpyruvate, and fluorobutanoate. It has a preference for the S-configuration at C2 of the electrophile.2 Publications

Catalytic activityi

4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate.1 Publication
2-dehydro-3-deoxy-6-phosphate-D-gluconate = pyruvate + D-glyceraldehyde 3-phosphate.1 Publication

Kineticsi

Kcat is 80 sec(-1) for KDPG, 0.012 sec(-1) for pyruvate and 0.0004 sec(-1) for 2-oxobutyrate.

  1. KM=0.1 mM for KDPG2 Publications
  2. KM=9 mM for 2-oxobutyrate2 Publications
  3. KM=10 mM for pyruvate2 Publications

    Pathway:i2-dehydro-3-deoxy-D-gluconate degradation

    This protein is involved in step 2 of the subpathway that synthesizes D-glyceraldehyde 3-phosphate and pyruvate from 2-dehydro-3-deoxy-D-gluconate.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. 2-dehydro-3-deoxygluconokinase (kdgK)
    2. KHG/KDPG aldolase (eda)
    This subpathway is part of the pathway 2-dehydro-3-deoxy-D-gluconate degradation, which is itself part of Carbohydrate acid metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes D-glyceraldehyde 3-phosphate and pyruvate from 2-dehydro-3-deoxy-D-gluconate, the pathway 2-dehydro-3-deoxy-D-gluconate degradation and in Carbohydrate acid metabolism.

    Pathway:iglyoxylate and dicarboxylate metabolism

    This protein is involved in the pathway glyoxylate and dicarboxylate metabolism, which is part of Carbohydrate metabolism.
    View all proteins of this organism that are known to be involved in the pathway glyoxylate and dicarboxylate metabolism and in Carbohydrate metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei45 – 451Proton acceptor
    Active sitei49 – 491
    Binding sitei49 – 491Substrate1 Publication
    Binding sitei73 – 731Substrate1 Publication
    Active sitei133 – 1331Schiff-base intermediate with substrate
    Binding sitei133 – 1331Substrate (covalent)1 Publication
    Binding sitei161 – 1611Substrate1 Publication
    Sitei161 – 1611Plays a major role in determining the stereoselectivity
    Binding sitei163 – 1631Substrate; via amide nitrogen1 Publication
    Binding sitei184 – 1841Substrate1 Publication

    GO - Molecular functioni

    • 2-dehydro-3-deoxy-phosphogluconate aldolase activity Source: EcoliWiki
    • 4-hydroxy-2-oxoglutarate aldolase activity Source: UniProtKB
    • identical protein binding Source: IntAct
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Schiff base

    Enzyme and pathway databases

    BioCyciEcoCyc:KDPGALDOL-4OH2OXOGLUTARALDOL-MONOMER.
    ECOL316407:JW1839-MONOMER.
    MetaCyc:KDPGALDOL-4OH2OXOGLUTARALDOL-MONOMER.
    BRENDAi4.1.2.14. 2026.
    4.1.3.42. 2026.
    UniPathwayiUPA00227.
    UPA00856; UER00829.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    KHG/KDPG aldolase
    Including the following 2 domains:
    4-hydroxy-2-oxoglutarate aldolase (EC:4.1.3.16)
    Alternative name(s):
    2-keto-4-hydroxyglutarate aldolase
    Short name:
    KHG-aldolase
    2-dehydro-3-deoxy-phosphogluconate aldolase (EC:4.1.2.14)
    Alternative name(s):
    2-keto-3-deoxy-6-phosphogluconate aldolase
    Short name:
    KDPG-aldolase
    Phospho-2-dehydro-3-deoxygluconate aldolase
    Phospho-2-keto-3-deoxygluconate aldolase
    Gene namesi
    Name:eda
    Synonyms:hga, kdgA
    Ordered Locus Names:b1850, JW1839
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10256. eda.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Cells lacking this gene lose KHG aldolase activity.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi45 – 451E → N: 50-fold decrease in catalytic efficiency and 6-fold decrease of binding affinity. 2 Publications
    Mutagenesisi133 – 1331K → Q: Absence of aldolase activity. Shows a markedly altered substrate specificity relative to the wild-type, with an enhanced activity against pyridine carboxaldehyde, benzaldehyde, and alpha-ketobutyrate; when associated with k-161. 1 Publication
    Mutagenesisi161 – 1611T → K: Shows activity significantly greater than wild-type. Shows a markedly altered substrate specificity relative to the wild-type, with an enhanced activity against pyridine carboxaldehyde, benzaldehyde, and alpha-ketobutyrate; when associated with Q-133. 2 Publications
    Mutagenesisi161 – 1611T → V: Little stereoselectivity, accepting KDPG and KDPGal as substrate with roughly equal efficacy. It strongly diminishes the activity against KDPG and slightly increases activity against KDPGal. 2 Publications
    Mutagenesisi168 – 1681N → S: Shows activity significantly greater than wild-type. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 213213KHG/KDPG aldolasePRO_0000201037Add
    BLAST

    Proteomic databases

    PaxDbiP0A955.
    PRIDEiP0A955.

    2D gel databases

    SWISS-2DPAGEP0A955.

    Expressioni

    Inductioni

    Constitutive, three-fold induction occurs for growth on gluconate and two-fold for growth on hexuronic acids.1 Publication

    Interactioni

    Subunit structurei

    Homotrimer.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-558114,EBI-558114

    Protein-protein interaction databases

    DIPiDIP-36196N.
    IntActiP0A955. 9 interactions.
    STRINGi511145.b1850.

    Structurei

    Secondary structure

    1
    213
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi8 – 136Combined sources
    Beta strandi16 – 216Combined sources
    Helixi26 – 283Combined sources
    Helixi29 – 3810Combined sources
    Beta strandi43 – 486Combined sources
    Helixi53 – 6311Combined sources
    Beta strandi67 – 737Combined sources
    Helixi77 – 8610Combined sources
    Beta strandi91 – 955Combined sources
    Helixi98 – 1069Combined sources
    Beta strandi107 – 1093Combined sources
    Beta strandi111 – 1177Combined sources
    Helixi118 – 1269Combined sources
    Beta strandi131 – 1344Combined sources
    Turni135 – 1417Combined sources
    Helixi142 – 1509Combined sources
    Beta strandi157 – 1637Combined sources
    Turni166 – 1683Combined sources
    Helixi169 – 1735Combined sources
    Beta strandi181 – 1833Combined sources
    Helixi184 – 1863Combined sources
    Helixi189 – 1946Combined sources
    Helixi197 – 21014Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EUAX-ray1.95A/B/C1-213[»]
    1EUNX-ray2.00A/B/C1-213[»]
    1FQ0X-ray2.10A/B/C1-213[»]
    1FWRX-ray2.70A/B/C1-213[»]
    1WAUX-ray2.80A1-213[»]
    1WBHX-ray1.55A/B/C1-213[»]
    2C0AX-ray1.55A/B/C1-213[»]
    ProteinModelPortaliP0A955.
    SMRiP0A955. Positions 1-213.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0A955.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 92Substrate binding

    Sequence similaritiesi

    Belongs to the KHG/KDPG aldolase family.Curated

    Phylogenomic databases

    eggNOGiCOG0800.
    HOGENOMiHOG000233114.
    InParanoidiP0A955.
    KOiK01625.
    OMAiKFFPAEY.
    OrthoDBiEOG67DPKT.
    PhylomeDBiP0A955.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    InterProiIPR000887. Aldlse_KDPG_KHG.
    IPR013785. Aldolase_TIM.
    [Graphical view]
    PfamiPF01081. Aldolase. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR01182. eda. 1 hit.
    PROSITEiPS00159. ALDOLASE_KDPG_KHG_1. 1 hit.
    PS00160. ALDOLASE_KDPG_KHG_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0A955-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKNWKTSAES ILTTGPVVPV IVVKKLEHAV PMAKALVAGG VRVLEVTLRT
    60 70 80 90 100
    ECAVDAIRAI AKEVPEAIVG AGTVLNPQQL AEVTEAGAQF AISPGLTEPL
    110 120 130 140 150
    LKAATEGTIP LIPGISTVSE LMLGMDYGLK EFKFFPAEAN GGVKALQAIA
    160 170 180 190 200
    GPFSQVRFCP TGGISPANYR DYLALKSVLC IGGSWLVPAD ALEAGDYDRI
    210
    TKLAREAVEG AKL
    Length:213
    Mass (Da):22,284
    Last modified:July 19, 2005 - v1
    Checksum:iCC8D51B50480D0B7
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X68871 Genomic DNA. Translation: CAA48732.1.
    M87458 Genomic DNA. Translation: AAA23723.1.
    L20897 Genomic DNA. Translation: AAA23862.1.
    X63694 Genomic DNA. Translation: CAA45222.1.
    U00096 Genomic DNA. Translation: AAC74920.1.
    AP009048 Genomic DNA. Translation: BAA15658.1.
    PIRiB42986. ADECOG.
    RefSeqiNP_416364.1. NC_000913.3.
    WP_000800512.1. NZ_CP010445.1.

    Genome annotation databases

    EnsemblBacteriaiAAC74920; AAC74920; b1850.
    BAA15658; BAA15658; BAA15658.
    GeneIDi946367.
    KEGGieco:b1850.
    PATRICi32119021. VBIEscCol129921_1928.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X68871 Genomic DNA. Translation: CAA48732.1.
    M87458 Genomic DNA. Translation: AAA23723.1.
    L20897 Genomic DNA. Translation: AAA23862.1.
    X63694 Genomic DNA. Translation: CAA45222.1.
    U00096 Genomic DNA. Translation: AAC74920.1.
    AP009048 Genomic DNA. Translation: BAA15658.1.
    PIRiB42986. ADECOG.
    RefSeqiNP_416364.1. NC_000913.3.
    WP_000800512.1. NZ_CP010445.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EUAX-ray1.95A/B/C1-213[»]
    1EUNX-ray2.00A/B/C1-213[»]
    1FQ0X-ray2.10A/B/C1-213[»]
    1FWRX-ray2.70A/B/C1-213[»]
    1WAUX-ray2.80A1-213[»]
    1WBHX-ray1.55A/B/C1-213[»]
    2C0AX-ray1.55A/B/C1-213[»]
    ProteinModelPortaliP0A955.
    SMRiP0A955. Positions 1-213.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-36196N.
    IntActiP0A955. 9 interactions.
    STRINGi511145.b1850.

    2D gel databases

    SWISS-2DPAGEP0A955.

    Proteomic databases

    PaxDbiP0A955.
    PRIDEiP0A955.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC74920; AAC74920; b1850.
    BAA15658; BAA15658; BAA15658.
    GeneIDi946367.
    KEGGieco:b1850.
    PATRICi32119021. VBIEscCol129921_1928.

    Organism-specific databases

    EchoBASEiEB0252.
    EcoGeneiEG10256. eda.

    Phylogenomic databases

    eggNOGiCOG0800.
    HOGENOMiHOG000233114.
    InParanoidiP0A955.
    KOiK01625.
    OMAiKFFPAEY.
    OrthoDBiEOG67DPKT.
    PhylomeDBiP0A955.

    Enzyme and pathway databases

    UniPathwayiUPA00227.
    UPA00856; UER00829.
    BioCyciEcoCyc:KDPGALDOL-4OH2OXOGLUTARALDOL-MONOMER.
    ECOL316407:JW1839-MONOMER.
    MetaCyc:KDPGALDOL-4OH2OXOGLUTARALDOL-MONOMER.
    BRENDAi4.1.2.14. 2026.
    4.1.3.42. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP0A955.
    PROiP0A955.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    InterProiIPR000887. Aldlse_KDPG_KHG.
    IPR013785. Aldolase_TIM.
    [Graphical view]
    PfamiPF01081. Aldolase. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR01182. eda. 1 hit.
    PROSITEiPS00159. ALDOLASE_KDPG_KHG_1. 1 hit.
    PS00160. ALDOLASE_KDPG_KHG_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The complete amino acid sequence and identification of the active-site arginine peptide of Escherichia coli 2-keto-4-hydroxyglutarate aldolase."
      Vlahos C.J., Dekker E.E.
      J. Biol. Chem. 263:11683-11691(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE, ACTIVE SITE.
      Strain: K12.
    2. "Cloning, nucleotide sequence, overexpression, and inactivation of the Escherichia coli 2-keto-4-hydroxyglutarate aldolase gene."
      Patil R.V., Dekker E.E.
      J. Bacteriol. 174:102-107(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A KHG-ALDOLASE, DISRUPTION PHENOTYPE.
    3. "Molecular characterization of the Entner-Doudoroff pathway in Escherichia coli: sequence analysis and localization of promoters for the edd-eda operon."
      Egan S.E., Fliege R., Tong S., Shibata A., Wolf R.E. Jr., Conway T.
      J. Bacteriol. 174:4638-4646(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Purine and one-carbon metabolism in Escherichia coli K12: DNA sequence of a second GAR transformylase."
      Smith J.M., Nygaard P.
      Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    5. "Sequence of the Escherichia coli K-12 edd and eda genes of the Entner-Doudoroff pathway."
      Carter A.T., Pearson B.M., Dickinson J.R., Lancashire W.E.
      Gene 130:155-156(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    8. "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.
    9. "Active-site residues of 2-keto-4-hydroxyglutarate aldolase from Escherichia coli. Bromopyruvate inactivation and labeling of glutamate 45."
      Vlahos C.J., Dekker E.E.
      J. Biol. Chem. 265:20384-20389(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE.
    10. "Escherichia coli proteome analysis using the gene-protein database."
      VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.
      Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY 2D-GEL.
    11. "Characterization and crystal structure of Escherichia coli KDPGal aldolase."
      Walters M.J., Srikannathasan V., McEwan A.R., Naismith J.H., Fierke C.A., Toone E.J.
      Bioorg. Med. Chem. 16:710-720(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A KDPG-ALDOLASE, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-45 AND THR-161, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, INDUCTION.
    12. "Covalent intermediate trapped in 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase structure at 1.95-A resolution."
      Allard J., Grochulski P., Sygusch J.
      Proc. Natl. Acad. Sci. U.S.A. 98:3679-3684(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH SUSBTRATE, REACTION MECHANISM, SUBUNIT.
    13. "Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli."
      Wymer N., Buchanan L.V., Henderson D., Mehta N., Botting C.H., Pocivavsek L., Fierke C.A., Toone E.J., Naismith J.H.
      Structure 9:1-9(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF WILD-TYPE AND DOUBLE MUTANT IN COMPLEX WITH SUSBTRATE, MUTAGENESIS OF LYS-133; THR-161 AND ASN-168, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    14. Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF WILD-TYPE AND MUTANT IN COMPLEX WITH SUBSTRATE, MUTAGENESIS OF GLU-45, REACTION MECHANISM, SUBUNIT.

    Entry informationi

    Entry nameiALKH_ECOLI
    AccessioniPrimary (citable) accession number: P0A955
    Secondary accession number(s): P10177
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2005
    Last sequence update: July 19, 2005
    Last modified: July 22, 2015
    This is version 88 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme, 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.