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Protein

Diaminopimelate epimerase

Gene

dapF

Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the stereoinversion of LL-2,6-diaminoheptanedioate (L,L-DAP) to meso-diaminoheptanedioate (meso-DAP), a precursor of L-lysine and an essential component of the bacterial peptidoglycan. Only accepts DAP isomers with the L configuration.1 Publication

Catalytic activityi

LL-2,6-diaminoheptanedioate = meso-diaminoheptanedioate.1 Publication

Enzyme regulationi

Inhibited by LL-aziridino (LL-AziDAP), DL-aziridino (DL-AziDAP), (2S,3R,6S)-2,6-diamino-3-fluoropimelate (L,L-3-fluoro-DAP) and (2R,3S,6S)-2,6-diamino-3-fluoropimelate (D,L-3-fluoro-DAP).2 Publications

Kineticsi

Kcat is 128 and 82 (sec-1) for L,L-DAP and D,L-DAP, respectively.

  1. KM=0.7 mM for L,L-DAP (at pH 7.8)1 Publication
  2. KM=1.1 mM for D,L-DAP (at pH 7.8)1 Publication

    Pathway: L-lysine biosynthesis via DAP pathway

    This protein is involved in step 1 of the subpathway that synthesizes DL-2,6-diaminopimelate from LL-2,6-diaminopimelate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Diaminopimelate epimerase (dapF)
    This subpathway is part of the pathway L-lysine biosynthesis via DAP pathway, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes DL-2,6-diaminopimelate from LL-2,6-diaminopimelate, the pathway L-lysine biosynthesis via DAP pathway and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei11 – 111Substrate
    Binding sitei44 – 441Substrate
    Binding sitei64 – 641Substrate
    Active sitei73 – 731Proton donor/acceptor
    Binding sitei157 – 1571Substrate
    Sitei159 – 1591Important for catalytic activitySequence Analysis
    Binding sitei190 – 1901Substrate
    Sitei208 – 2081Important for catalytic activitySequence Analysis
    Active sitei217 – 2171Proton donor/acceptor

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Isomerase

    Keywords - Biological processi

    Amino-acid biosynthesis, Lysine biosynthesis

    Enzyme and pathway databases

    BRENDAi5.1.1.7. 2529.
    UniPathwayiUPA00034; UER00025.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diaminopimelate epimerase (EC:5.1.1.7)
    Short name:
    DAP epimerase
    Alternative name(s):
    PLP-Independent Amino Acid Racemases
    Gene namesi
    Name:dapF
    Ordered Locus Names:HI_0750
    OrganismiHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
    Taxonomic identifieri71421 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPasteurellalesPasteurellaceaeHaemophilus
    ProteomesiUP000000579 Componenti: Chromosome

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi73 – 731C → A: Inactive as epimerases, but it is able to rapidly catalyze the HF eliminatio via abstraction of the C-2 hydrogen of the D,L-3-fluoro-DAP analog and is essentially unable to catalyze the same elimination with the L,L-3-fluoro-DAP analog. 2 Publications
    Mutagenesisi73 – 731C → S: It is able to catalyze both epimerization of DAP and HF elimination of L,L-3-fluoro-DAP and D,L-3-fluoro-DAP. Able to slowly eliminate HF but does not catalyze epimerization; when associated with S-217. 2 Publications
    Mutagenesisi217 – 2171C → A: Inactive as epimerases. It is able to rapidly catalyze the HF eliminatio via abstraction of the C-2 hydrogen of the L,L-3-fluoro-DAP analog and is essentially unable to catalyze the same elimination with the D,L-3-fluoro-DAP analog. 2 Publications
    Mutagenesisi217 – 2171C → S: It is able to catalyze both epimerization of DAP and HF elimination of L,L-3-fluoro-DAP and D,L-3-fluoro-DAP. Able to slowly eliminate HF but does not catalyze epimerization; when associated with S-73. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 274274Diaminopimelate epimerasePRO_0000149842Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi73 ↔ 2171 Publication

    Keywords - PTMi

    Disulfide bond

    Interactioni

    Subunit structurei

    Monomer.3 Publications

    Protein-protein interaction databases

    STRINGi71421.HI0750.

    Structurei

    Secondary structure

    1
    274
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 87Combined sources
    Beta strandi11 – 177Combined sources
    Beta strandi19 – 213Combined sources
    Helixi27 – 348Combined sources
    Turni36 – 383Combined sources
    Beta strandi43 – 497Combined sources
    Beta strandi56 – 649Combined sources
    Beta strandi69 – 713Combined sources
    Helixi74 – 8613Combined sources
    Beta strandi93 – 986Combined sources
    Beta strandi103 – 1086Combined sources
    Beta strandi114 – 1174Combined sources
    Helixi125 – 1273Combined sources
    Beta strandi137 – 1426Combined sources
    Beta strandi147 – 16317Combined sources
    Turni167 – 1693Combined sources
    Helixi172 – 1809Combined sources
    Beta strandi190 – 1989Combined sources
    Beta strandi201 – 2088Combined sources
    Turni209 – 2113Combined sources
    Helixi218 – 23013Combined sources
    Beta strandi236 – 2427Combined sources
    Beta strandi245 – 2517Combined sources
    Beta strandi258 – 2625Combined sources
    Beta strandi265 – 2717Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BWZX-ray2.72A1-274[»]
    1GQZX-ray1.75A1-274[»]
    2GKEX-ray1.35A1-274[»]
    2GKJX-ray1.70A1-274[»]
    2Q9HX-ray2.30A1-274[»]
    2Q9JX-ray2.20A1-274[»]
    ProteinModelPortaliP44859.
    SMRiP44859. Positions 1-274.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP44859.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 92Substrate
    Regioni73 – 753Substrate binding
    Regioni208 – 2092Substrate binding
    Regioni218 – 2192Substrate binding

    Sequence similaritiesi

    Belongs to the diaminopimelate epimerase family.Curated

    Phylogenomic databases

    eggNOGiCOG0253.
    KOiK01778.
    OMAiMKFTKMH.
    OrthoDBiEOG6ND0M5.
    PhylomeDBiP44859.

    Family and domain databases

    HAMAPiMF_00197. DAP_epimerase.
    InterProiIPR018510. DAP_epimerase_AS.
    IPR001653. DAP_epimerase_DapF.
    [Graphical view]
    PANTHERiPTHR31689. PTHR31689. 1 hit.
    PfamiPF01678. DAP_epimerase. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR00652. DapF. 1 hit.
    PROSITEiPS01326. DAP_EPIMERASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P44859-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQFSKMHGLG NDFVVVDGVT QNVFFTPETI RRLANRHCGI GFDQLLIVEA
    60 70 80 90 100
    PYDPELDFHY RIFNADGSEV SQCGNGARCF ARFVTLKGLT NKKDISVSTQ
    110 120 130 140 150
    KGNMVLTVKD DNQIRVNMGE PIWEPAKIPF TANKFEKNYI LRTDIQTVLC
    160 170 180 190 200
    GAVSMGNPHC VVQVDDIQTA NVEQLGPLLE SHERFPERVN AGFMQIINKE
    210 220 230 240 250
    HIKLRVYERG AGETQACGSG ACAAVAVGIM QGLLNNNVQV DLPGGSLMIE
    260 270
    WNGVGHPLYM TGEATHIYDG FITL
    Length:274
    Mass (Da):30,249
    Last modified:November 1, 1995 - v1
    Checksum:i321B3CDAFFE81EDA
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L42023 Genomic DNA. Translation: AAC22409.1.
    PIRiF64090.
    RefSeqiNP_438909.1. NC_000907.1.
    WP_005655521.1. NC_000907.1.

    Genome annotation databases

    EnsemblBacteriaiAAC22409; AAC22409; HI_0750.
    GeneIDi949560.
    KEGGihin:HI0750.
    PATRICi20190143. VBIHaeInf48452_0787.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L42023 Genomic DNA. Translation: AAC22409.1.
    PIRiF64090.
    RefSeqiNP_438909.1. NC_000907.1.
    WP_005655521.1. NC_000907.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BWZX-ray2.72A1-274[»]
    1GQZX-ray1.75A1-274[»]
    2GKEX-ray1.35A1-274[»]
    2GKJX-ray1.70A1-274[»]
    2Q9HX-ray2.30A1-274[»]
    2Q9JX-ray2.20A1-274[»]
    ProteinModelPortaliP44859.
    SMRiP44859. Positions 1-274.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi71421.HI0750.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC22409; AAC22409; HI_0750.
    GeneIDi949560.
    KEGGihin:HI0750.
    PATRICi20190143. VBIHaeInf48452_0787.

    Phylogenomic databases

    eggNOGiCOG0253.
    KOiK01778.
    OMAiMKFTKMH.
    OrthoDBiEOG6ND0M5.
    PhylomeDBiP44859.

    Enzyme and pathway databases

    UniPathwayiUPA00034; UER00025.
    BRENDAi5.1.1.7. 2529.

    Miscellaneous databases

    EvolutionaryTraceiP44859.

    Family and domain databases

    HAMAPiMF_00197. DAP_epimerase.
    InterProiIPR018510. DAP_epimerase_AS.
    IPR001653. DAP_epimerase_DapF.
    [Graphical view]
    PANTHERiPTHR31689. PTHR31689. 1 hit.
    PfamiPF01678. DAP_epimerase. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR00652. DapF. 1 hit.
    PROSITEiPS01326. DAP_EPIMERASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
    2. "Chemical mechanism of Haemophilus influenzae diaminopimelate epimerase."
      Koo C.W., Blanchard J.S.
      Biochemistry 38:4416-4422(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, BIOPHYSICOCHEMICAL PROPERTIES.
    3. "Identification of active site cysteine residues that function as general bases: diaminopimelate epimerase."
      Koo C.W., Sutherland A., Vederas J.C., Blanchard J.S.
      J. Am. Chem. Soc. 122:6122-6123(2000)
      Cited for: MUTAGENESIS OF CYS-73 AND CYS-217, ACTIVE SITE, ENZYME REGULATION.
    4. "Structural symmetry: the three-dimensional structure of Haemophilus influenzae diaminopimelate epimerase."
      Cirilli M., Zheng R., Scapin G., Blanchard J.S.
      Biochemistry 37:16452-16458(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.72 ANGSTROMS), ACTIVE SITE, DISULFIDE BOND, SUBUNIT.
    5. "Refinement of Haemophilus influenzae diaminopimelic acid epimerase (DapF) at 1.75 A resolution suggests a mechanism for stereocontrol during catalysis."
      Lloyd A.J., Huyton T., Turkenburg J., Roper D.I.
      Acta Crystallogr. D 60:397-400(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), REACTION MECHANISM.
    6. "Structural insights into stereochemical inversion by diaminopimelate epimerase: an antibacterial drug target."
      Pillai B., Cherney M.M., Diaper C.M., Sutherland A., Blanchard J.S., Vederas J.C., James M.N.
      Proc. Natl. Acad. Sci. U.S.A. 103:8668-8673(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS, SUBSTRATE SPECIFICITY, ENZYME REGULATION.
    7. "Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase."
      Pillai B., Cherney M., Diaper C.M., Sutherland A., Blanchard J.S., Vederas J.C., James M.N.
      Biochem. Biophys. Res. Commun. 363:547-553(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT SER-73 AND SER-217 IN COMPLEX WITH SUBSTRATE ANALOGS, MUTAGENESIS OF CYS-73 AND CYS-217.

    Entry informationi

    Entry nameiDAPF_HAEIN
    AccessioniPrimary (citable) accession number: P44859
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: May 27, 2015
    This is version 109 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, Reference proteome

    Documents

    1. Haemophilus influenzae
      Haemophilus influenzae (strain Rd): entries and gene names
    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.