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Protein

Vancomycin/teicoplanin A-type resistance protein VanA

Gene

vanA

Organism
Enterococcus faecium (Streptococcus faecium)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for high-level resistance to glycopeptide antibiotics. D-Ala--D-Ala ligase of altered specificity which catalyzes ester bond formation between D-Ala and various D-hydroxy acids; produces a peptidoglycan which does not terminate in D-alanine but in D-lactate, thus preventing vancomycin or teicoplanin binding.1 Publication

Catalytic activityi

D-alanine + (R)-lactate + ATP = D-alanyl-(R)-lactate + ADP + phosphate.1 Publication

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium or manganese ions per subunit.By similarity

Kineticsi

  1. KM=7.1 mM for D-lactate1 Publication
  2. KM=3.8 mM for D-alanine1 Publication
  3. KM=0.6 mM for 2-hydroxybutyrate1 Publication
  4. KM=3.2 mM for 2-hydroxyvalerate1 Publication
  5. KM=11 mM for 2-hydroxycaproate1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei133 – 1331ATP
    Binding sitei241 – 2411ATP; via amide nitrogen
    Binding sitei244 – 2441Substrate
    Metal bindingi305 – 3051Magnesium 11 Publication
    Metal bindingi305 – 3051Magnesium 21 Publication
    Metal bindingi307 – 3071Magnesium 21 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi169 – 1713ATP
    Nucleotide bindingi177 – 1782ATP
    Nucleotide bindingi207 – 2148ATP
    Nucleotide bindingi304 – 3052ATP

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Antibiotic resistance, Cell shape, Cell wall biogenesis/degradation, Peptidoglycan synthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15466.
    BRENDAi6.1.2.1. 2096.
    SABIO-RKP25051.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Vancomycin/teicoplanin A-type resistance protein VanA (EC:6.1.2.1)
    Alternative name(s):
    D-alanine--D-lactate ligase
    VanA ligase
    Gene namesi
    Name:vanA
    Encoded oniPlasmid pIP8160 Publication
    OrganismiEnterococcus faecium (Streptococcus faecium)
    Taxonomic identifieri1352 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesEnterococcaceaeEnterococcus

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Chemistry

    ChEMBLiCHEMBL6037.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 343343Vancomycin/teicoplanin A-type resistance protein VanAPRO_0000177917Add
    BLAST

    Expressioni

    Inductioni

    By vancomycin, mediated by VanS/VanR.

    Interactioni

    Chemistry

    BindingDBiP25051.

    Structurei

    Secondary structure

    1
    343
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 118Combined sources
    Helixi17 – 3014Combined sources
    Turni33 – 353Combined sources
    Beta strandi36 – 438Combined sources
    Beta strandi49 – 535Combined sources
    Beta strandi65 – 695Combined sources
    Turni73 – 753Combined sources
    Beta strandi77 – 826Combined sources
    Beta strandi85 – 906Combined sources
    Beta strandi92 – 965Combined sources
    Turni101 – 1033Combined sources
    Beta strandi104 – 1063Combined sources
    Helixi107 – 1159Combined sources
    Beta strandi119 – 1213Combined sources
    Helixi124 – 1318Combined sources
    Helixi133 – 14210Combined sources
    Beta strandi150 – 1534Combined sources
    Helixi161 – 1633Combined sources
    Beta strandi168 – 1747Combined sources
    Turni177 – 1804Combined sources
    Beta strandi182 – 1843Combined sources
    Helixi187 – 1893Combined sources
    Helixi190 – 1978Combined sources
    Turni198 – 2003Combined sources
    Beta strandi202 – 2087Combined sources
    Beta strandi212 – 22211Combined sources
    Beta strandi232 – 2398Combined sources
    Helixi243 – 2453Combined sources
    Beta strandi246 – 2483Combined sources
    Helixi249 – 2513Combined sources
    Beta strandi254 – 2585Combined sources
    Helixi266 – 28217Combined sources
    Beta strandi286 – 29510Combined sources
    Beta strandi301 – 3099Combined sources
    Helixi317 – 3248Combined sources
    Helixi329 – 34113Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E4EX-ray2.50A/B1-343[»]
    ProteinModelPortaliP25051.
    SMRiP25051. Positions 2-342.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP25051.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini137 – 338202ATP-graspAdd
    BLAST

    Sequence similaritiesi

    Belongs to the D-alanine--D-alanine ligase family.Curated
    Contains 1 ATP-grasp domain.Curated

    Phylogenomic databases

    KOiK15739.

    Family and domain databases

    Gene3Di3.30.1490.20. 1 hit.
    3.30.470.20. 2 hits.
    3.40.50.20. 1 hit.
    HAMAPiMF_00047. Dala_Dala_lig. 1 hit.
    InterProiIPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    IPR000291. D-Ala_lig_Van_CS.
    IPR005905. D_ala_D_ala.
    IPR011095. Dala_Dala_lig_C.
    IPR011127. Dala_Dala_lig_N.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF07478. Dala_Dala_lig_C. 1 hit.
    PF01820. Dala_Dala_lig_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF039102. Ddl/VanB. 1 hit.
    SUPFAMiSSF52440. SSF52440. 1 hit.
    TIGRFAMsiTIGR01205. D_ala_D_alaTIGR. 1 hit.
    PROSITEiPS50975. ATP_GRASP. 1 hit.
    PS00843. DALA_DALA_LIGASE_1. 1 hit.
    PS00844. DALA_DALA_LIGASE_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P25051-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MNRIKVAILF GGCSEEHDVS VKSAIEIAAN INKEKYEPLY IGITKSGVWK
    60 70 80 90 100
    MCEKPCAEWE NDNCYSAVLS PDKKMHGLLV KKNHEYEINH VDVAFSALHG
    110 120 130 140 150
    KSGEDGSIQG LFELSGIPFV GCDIQSSAIC MDKSLTYIVA KNAGIATPAF
    160 170 180 190 200
    WVINKDDRPV AATFTYPVFV KPARSGSSFG VKKVNSADEL DYAIESARQY
    210 220 230 240 250
    DSKILIEQAV SGCEVGCAVL GNSAALVVGE VDQIRLQYGI FRIHQEVEPE
    260 270 280 290 300
    KGSENAVITV PADLSAEERG RIQETAKKIY KALGCRGLAR VDMFLQDNGR
    310 320 330 340
    IVLNEVNTLP GFTSYSRYPR MMAAAGIALP ELIDRLIVLA LKG
    Length:343
    Mass (Da):37,443
    Last modified:May 1, 1992 - v1
    Checksum:iAAA48E3B2AD48E03
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X56895 Genomic DNA. Translation: CAA40215.1.
    M97297 Genomic DNA. Translation: AAA65956.1.
    PIRiS12254. CESOVM.
    RefSeqiWP_001079845.1. NZ_LNMX01000005.1.
    YP_001019035.1. NC_008821.1.
    YP_001974796.1. NC_010980.1.
    YP_002128399.1. NC_011140.1.
    YP_976077.1. NC_008768.1.

    Genome annotation databases

    GeneIDi4670249.
    4783144.
    6385877.
    6779647.
    KEGGiag:CAA40215.
    pg:4670249.
    pg:4783144.
    pg:6385877.
    pg:6779647.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X56895 Genomic DNA. Translation: CAA40215.1.
    M97297 Genomic DNA. Translation: AAA65956.1.
    PIRiS12254. CESOVM.
    RefSeqiWP_001079845.1. NZ_LNMX01000005.1.
    YP_001019035.1. NC_008821.1.
    YP_001974796.1. NC_010980.1.
    YP_002128399.1. NC_011140.1.
    YP_976077.1. NC_008768.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E4EX-ray2.50A/B1-343[»]
    ProteinModelPortaliP25051.
    SMRiP25051. Positions 2-342.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    BindingDBiP25051.
    ChEMBLiCHEMBL6037.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi4670249.
    4783144.
    6385877.
    6779647.
    KEGGiag:CAA40215.
    pg:4670249.
    pg:4783144.
    pg:6385877.
    pg:6779647.

    Phylogenomic databases

    KOiK15739.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15466.
    BRENDAi6.1.2.1. 2096.
    SABIO-RKP25051.

    Miscellaneous databases

    EvolutionaryTraceiP25051.
    PROiP25051.

    Family and domain databases

    Gene3Di3.30.1490.20. 1 hit.
    3.30.470.20. 2 hits.
    3.40.50.20. 1 hit.
    HAMAPiMF_00047. Dala_Dala_lig. 1 hit.
    InterProiIPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    IPR000291. D-Ala_lig_Van_CS.
    IPR005905. D_ala_D_ala.
    IPR011095. Dala_Dala_lig_C.
    IPR011127. Dala_Dala_lig_N.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF07478. Dala_Dala_lig_C. 1 hit.
    PF01820. Dala_Dala_lig_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF039102. Ddl/VanB. 1 hit.
    SUPFAMiSSF52440. SSF52440. 1 hit.
    TIGRFAMsiTIGR01205. D_ala_D_alaTIGR. 1 hit.
    PROSITEiPS50975. ATP_GRASP. 1 hit.
    PS00843. DALA_DALA_LIGASE_1. 1 hit.
    PS00844. DALA_DALA_LIGASE_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiVANA_ENTFC
    AccessioniPrimary (citable) accession number: P25051
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1992
    Last sequence update: May 1, 1992
    Last modified: June 8, 2016
    This is version 119 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, Direct protein sequencing, Plasmid

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. 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.