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Protein

Shikimate kinase

Gene

aroK

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate.2 Publications

Catalytic activityi

ATP + shikimate = ADP + shikimate 3-phosphate.

Cofactori

Mg2+2 PublicationsNote: Binds 1 Mg2+ ion per subunit.2 Publications

Kineticsi

  1. KM=410 µM for shikimate1 Publication
  2. KM=83 µM for ATP1 Publication

    Pathwayi: chorismate biosynthesis

    This protein is involved in step 5 of the subpathway that synthesizes chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate.
    Proteins known to be involved in the 7 steps of the subpathway in this organism are:
    1. Phospho-2-dehydro-3-deoxyheptonate aldolase (LH57_11870), Phospho-2-dehydro-3-deoxyheptonate aldolase AroG (aroG)
    2. 3-dehydroquinate synthase (aroB), 3-dehydroquinate synthase (aroB)
    3. 3-dehydroquinate dehydratase (aroQ), 3-dehydroquinate dehydratase (aroQ)
    4. no protein annotated in this organism
    5. Shikimate kinase (aroK), Shikimate kinase (aroK)
    6. 3-phosphoshikimate 1-carboxyvinyltransferase (aroA), 3-phosphoshikimate 1-carboxyvinyltransferase (aroA)
    7. Chorismate synthase (aroC), Chorismate synthase (aroC)
    This subpathway is part of the pathway chorismate biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate, the pathway chorismate biosynthesis and in Metabolic intermediate biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi16 – 161Magnesium
    Binding sitei34 – 341Substrate
    Binding sitei58 – 581Substrate
    Binding sitei80 – 801Substrate; via amide nitrogen
    Binding sitei117 – 1171ATP
    Binding sitei136 – 1361Substrate
    Binding sitei153 – 1531ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi12 – 176ATP

    GO - Molecular functioni

    • ATP binding Source: MTBBASE
    • magnesium ion binding Source: MTBBASE
    • shikimate kinase activity Source: MTBBASE

    GO - Biological processi

    • aromatic amino acid family biosynthetic process Source: GO_Central
    • chorismate biosynthetic process Source: Reactome
    • growth Source: MTBBASE
    • shikimate metabolic process Source: MTBBASE
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Amino-acid biosynthesis, Aromatic amino acid biosynthesis

    Keywords - Ligandi

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

    Enzyme and pathway databases

    ReactomeiR-MTU-964903. Chorismate via Shikimate Pathway.
    UniPathwayiUPA00053; UER00088.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Shikimate kinase (EC:2.7.1.71)
    Short name:
    SK
    Gene namesi
    Name:aroK
    Ordered Locus Names:Rv2539c
    ORF Names:MTCY159.17
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv2539c.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 176176Shikimate kinasePRO_0000192393Add
    BLAST

    Proteomic databases

    PaxDbiP9WPY3.

    Interactioni

    Subunit structurei

    Monomer.7 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv2539c.

    Structurei

    Secondary structure

    1
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 85Combined sources
    Helixi15 – 2612Combined sources
    Beta strandi30 – 323Combined sources
    Helixi33 – 419Combined sources
    Helixi45 – 528Combined sources
    Helixi54 – 7118Combined sources
    Beta strandi74 – 774Combined sources
    Helixi82 – 843Combined sources
    Helixi86 – 927Combined sources
    Beta strandi97 – 1015Combined sources
    Helixi104 – 1107Combined sources
    Turni111 – 1133Combined sources
    Helixi118 – 1214Combined sources
    Beta strandi122 – 1243Combined sources
    Helixi125 – 14319Combined sources
    Beta strandi145 – 1495Combined sources
    Beta strandi151 – 1533Combined sources
    Helixi155 – 1639Combined sources
    Helixi173 – 1764Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1L4UX-ray1.80A1-176[»]
    1L4YX-ray2.00A1-176[»]
    1U8AX-ray2.15A1-176[»]
    1WE2X-ray2.30A1-176[»]
    1ZYUX-ray2.90A1-176[»]
    2DFNX-ray1.93A1-176[»]
    2DFTX-ray2.80A/B/C/D1-176[»]
    2G1JX-ray2.00A/B1-176[»]
    2G1KX-ray1.75A1-176[»]
    2IYQX-ray1.80A1-176[»]
    2IYRX-ray1.98A/B1-176[»]
    2IYSX-ray1.40A1-176[»]
    2IYTX-ray1.47A1-176[»]
    2IYUX-ray1.85A1-176[»]
    2IYVX-ray1.35A1-176[»]
    2IYWX-ray1.85A1-176[»]
    2IYXX-ray1.49A1-176[»]
    2IYYX-ray1.62A1-176[»]
    2IYZX-ray2.30A1-176[»]
    3BAFX-ray2.25A1-176[»]
    4BQSX-ray2.15A/B/C1-176[»]
    ProteinModelPortaliP9WPY3.
    SMRiP9WPY3. Positions 2-176.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni112 – 12413LID domainAdd
    BLAST

    Domaini

    Consists of three domains: the CORE domain which forms the binding site for nucleotides, the LID domain which closes over the active site upon ATP or shikimate binding, and the substrate-binding domain which functions to recognize and bind shikimate.

    Sequence similaritiesi

    Belongs to the shikimate kinase family.Curated

    Phylogenomic databases

    eggNOGiENOG4105KHV. Bacteria.
    COG0703. LUCA.
    KOiK00891.
    OMAiLYRECAD.
    PhylomeDBiP9WPY3.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    HAMAPiMF_00109. Shikimate_kinase.
    InterProiIPR027417. P-loop_NTPase.
    IPR031322. Shikimate/glucono_kinase.
    IPR000623. Shikimate_kinase/TSH1.
    IPR023000. Shikimate_kinase_CS.
    [Graphical view]
    PfamiPF01202. SKI. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    PROSITEiPS01128. SHIKIMATE_KINASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P9WPY3-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAPKAVLVGL PGSGKSTIGR RLAKALGVGL LDTDVAIEQR TGRSIADIFA
    60 70 80 90 100
    TDGEQEFRRI EEDVVRAALA DHDGVLSLGG GAVTSPGVRA ALAGHTVVYL
    110 120 130 140 150
    EISAAEGVRR TGGNTVRPLL AGPDRAEKYR ALMAKRAPLY RRVATMRVDT
    160 170
    NRRNPGAVVR HILSRLQVPS PSEAAT
    Length:176
    Mass (Da):18,583
    Last modified:April 16, 2014 - v1
    Checksum:i208EE0C38F5186A1
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP45334.1.
    PIRiG70658.
    RefSeqiNP_217055.1. NC_000962.3.
    WP_003413021.1. NZ_KK339370.1.

    Genome annotation databases

    EnsemblBacteriaiCCP45334; CCP45334; Rv2539c.
    GeneIDi887434.
    KEGGimtu:Rv2539c.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP45334.1.
    PIRiG70658.
    RefSeqiNP_217055.1. NC_000962.3.
    WP_003413021.1. NZ_KK339370.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1L4UX-ray1.80A1-176[»]
    1L4YX-ray2.00A1-176[»]
    1U8AX-ray2.15A1-176[»]
    1WE2X-ray2.30A1-176[»]
    1ZYUX-ray2.90A1-176[»]
    2DFNX-ray1.93A1-176[»]
    2DFTX-ray2.80A/B/C/D1-176[»]
    2G1JX-ray2.00A/B1-176[»]
    2G1KX-ray1.75A1-176[»]
    2IYQX-ray1.80A1-176[»]
    2IYRX-ray1.98A/B1-176[»]
    2IYSX-ray1.40A1-176[»]
    2IYTX-ray1.47A1-176[»]
    2IYUX-ray1.85A1-176[»]
    2IYVX-ray1.35A1-176[»]
    2IYWX-ray1.85A1-176[»]
    2IYXX-ray1.49A1-176[»]
    2IYYX-ray1.62A1-176[»]
    2IYZX-ray2.30A1-176[»]
    3BAFX-ray2.25A1-176[»]
    4BQSX-ray2.15A/B/C1-176[»]
    ProteinModelPortaliP9WPY3.
    SMRiP9WPY3. Positions 2-176.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv2539c.

    Proteomic databases

    PaxDbiP9WPY3.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP45334; CCP45334; Rv2539c.
    GeneIDi887434.
    KEGGimtu:Rv2539c.

    Organism-specific databases

    TubercuListiRv2539c.

    Phylogenomic databases

    eggNOGiENOG4105KHV. Bacteria.
    COG0703. LUCA.
    KOiK00891.
    OMAiLYRECAD.
    PhylomeDBiP9WPY3.

    Enzyme and pathway databases

    UniPathwayiUPA00053; UER00088.
    ReactomeiR-MTU-964903. Chorismate via Shikimate Pathway.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    HAMAPiMF_00109. Shikimate_kinase.
    InterProiIPR027417. P-loop_NTPase.
    IPR031322. Shikimate/glucono_kinase.
    IPR000623. Shikimate_kinase/TSH1.
    IPR023000. Shikimate_kinase_CS.
    [Graphical view]
    PfamiPF01202. SKI. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    PROSITEiPS01128. SHIKIMATE_KINASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning and overexpression in soluble form of functional shikimate kinase and 5-enolpyruvylshikimate 3-phosphate synthase enzymes from Mycobacterium tuberculosis."
      Oliveira J.S., Pinto C.A., Basso L.A., Santos D.S.
      Protein Expr. Purif. 22:430-435(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBUNIT.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 25618 / H37Rv.
    3. "Crystallization and preliminary X-ray diffraction analysis of shikimate kinase from Mycobacterium tuberculosis in complex with MgADP."
      Gu Y., Reshetnikova L., Li Y., Yan H., Singh S.V., Ji X.
      Acta Crystallogr. D 57:1870-1871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CRYSTALLIZATION.
      Strain: ATCC 25618 / H37Rv.
    4. "targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis."
      Raman K., Yeturu K., Chandra N.
      BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Strain: ATCC 25618 / H37Rv.
    6. "Crystal structure of shikimate kinase from Mycobacterium tuberculosis reveals the dynamic role of the LID domain in catalysis."
      Gu Y., Reshetnikova L., Li Y., Wu Y., Yan H., Singh S.V., Ji X.
      J. Mol. Biol. 319:779-789(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH MG-ADP, COFACTOR, KINETIC PARAMETERS.
      Strain: ATCC 25618 / H37Rv.
    7. "Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid."
      Pereira J.H., de Oliveira J.S., Canduri F., Dias M.V.B., Palma M.S., Basso L.A., Santos D.S., de Azevedo W.F. Jr.
      Acta Crystallogr. D 60:2310-2319(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND MG-ADP, COFACTOR.
    8. "Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase."
      Dhaliwal B., Nichols C.E., Ren J., Lockyer M., Charles I.G., Hawkins A.R., Stammers D.K.
      FEBS Lett. 574:49-54(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND ADP.
    9. "Crystal structure of Mycobacterium tuberculosis shikimate kinase in complex with shikimic acid and an ATP analogue."
      Gan J., Gu Y., Li Y., Yan H., Ji X.
      Biochemistry 45:8539-8545(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH SUBSTRATES.
      Strain: ATCC 25618 / H37Rv.
    10. "Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis."
      Hartmann M.D., Bourenkov G.P., Oberschall A., Strizhov N., Bartunik H.D.
      J. Mol. Biol. 364:411-423(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH SUBSTRATES AND PRODUCTS, FUNCTION, REACTION MECHANISM.
      Strain: ATCC 25618 / H37Rv.
    11. "Effects of the magnesium and chloride ions and shikimate on the structure of shikimate kinase from Mycobacterium tuberculosis."
      Dias M.V.B., Faim L.M., Vasconcelos I.B., de Oliveira J.S., Basso L.A., Santos D.S., de Azevedo W.F. Jr.
      Acta Crystallogr. F 63:1-6(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND MG-ADP.

    Entry informationi

    Entry nameiAROK_MYCTU
    AccessioniPrimary (citable) accession number: P9WPY3
    Secondary accession number(s): L0TBI1, P0A4Z2, P95014
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: February 17, 2016
    This is version 20 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The phosphoryl transfer proceeds by an in-line associative mechanism. The random sequential binding of shikimate and nucleotide is associated with domain movements that suggest a synergic mechanism by which binding of the first substrate may enhance the affinity for the second substrate.
    Was identified as a high-confidence drug target.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
      Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: 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

    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.