AROK_MYCTU
ID AROK_MYCTU Reviewed; 176 AA.
AC P9WPY3; L0TBI1; P0A4Z2; P95014;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Shikimate kinase {ECO:0000303|PubMed:11483005};
DE Short=SK;
DE EC=2.7.1.71 {ECO:0000269|PubMed:11483005, ECO:0000269|PubMed:17020768};
GN Name=aroK; OrderedLocusNames=Rv2539c; ORFNames=MTCY159.17;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=11483005; DOI=10.1006/prep.2001.1457;
RA Oliveira J.S., Pinto C.A., Basso L.A., Santos D.S.;
RT "Cloning and overexpression in soluble form of functional shikimate kinase
RT and 5-enolpyruvylshikimate 3-phosphate synthase enzymes from Mycobacterium
RT tuberculosis.";
RL Protein Expr. Purif. 22:430-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [3]
RP CRYSTALLIZATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11717501; DOI=10.1107/s0907444901014032;
RA Gu Y., Reshetnikova L., Li Y., Yan H., Singh S.V., Ji X.;
RT "Crystallization and preliminary X-ray diffraction analysis of shikimate
RT kinase from Mycobacterium tuberculosis in complex with MgADP.";
RL Acta Crystallogr. D 57:1870-1871(2001).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH MG-ADP, COFACTOR, AND
RP KINETIC PARAMETERS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12054870; DOI=10.1016/s0022-2836(02)00339-x;
RA Gu Y., Reshetnikova L., Li Y., Wu Y., Yan H., Singh S.V., Ji X.;
RT "Crystal structure of shikimate kinase from Mycobacterium tuberculosis
RT reveals the dynamic role of the LID domain in catalysis.";
RL J. Mol. Biol. 319:779-789(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND MG-ADP,
RP AND COFACTOR.
RX PubMed=15583379; DOI=10.1107/s090744490402517x;
RA Pereira J.H., de Oliveira J.S., Canduri F., Dias M.V.B., Palma M.S.,
RA Basso L.A., Santos D.S., de Azevedo W.F. Jr.;
RT "Structure of shikimate kinase from Mycobacterium tuberculosis reveals the
RT binding of shikimic acid.";
RL Acta Crystallogr. D 60:2310-2319(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND ADP.
RX PubMed=15358538; DOI=10.1016/j.febslet.2004.08.005;
RA Dhaliwal B., Nichols C.E., Ren J., Lockyer M., Charles I.G., Hawkins A.R.,
RA Stammers D.K.;
RT "Crystallographic studies of shikimate binding and induced conformational
RT changes in Mycobacterium tuberculosis shikimate kinase.";
RL FEBS Lett. 574:49-54(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH SUBSTRATES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16834327; DOI=10.1021/bi0606290;
RA Gan J., Gu Y., Li Y., Yan H., Ji X.;
RT "Crystal structure of Mycobacterium tuberculosis shikimate kinase in
RT complex with shikimic acid and an ATP analogue.";
RL Biochemistry 45:8539-8545(2006).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP SUBSTRATES AND PRODUCTS, FUNCTION, CATALYTIC ACTIVITY, AND REACTION
RP MECHANISM.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17020768; DOI=10.1016/j.jmb.2006.09.001;
RA Hartmann M.D., Bourenkov G.P., Oberschall A., Strizhov N., Bartunik H.D.;
RT "Mechanism of phosphoryl transfer catalyzed by shikimate kinase from
RT Mycobacterium tuberculosis.";
RL J. Mol. Biol. 364:411-423(2006).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEX WITH SHIKIMATE AND
RP MG-ADP.
RX PubMed=17183161; DOI=10.1107/s1744309106046823;
RA Dias M.V.B., Faim L.M., Vasconcelos I.B., de Oliveira J.S., Basso L.A.,
RA Santos D.S., de Azevedo W.F. Jr.;
RT "Effects of the magnesium and chloride ions and shikimate on the structure
RT of shikimate kinase from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 63:1-6(2007).
CC -!- FUNCTION: Catalyzes the specific phosphorylation of the 3-hydroxyl
CC group of shikimic acid using ATP as a cosubstrate.
CC {ECO:0000269|PubMed:11483005, ECO:0000269|PubMed:17020768}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + shikimate = 3-phosphoshikimate + ADP + H(+);
CC Xref=Rhea:RHEA:13121, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36208, ChEBI:CHEBI:145989, ChEBI:CHEBI:456216;
CC EC=2.7.1.71; Evidence={ECO:0000269|PubMed:11483005,
CC ECO:0000269|PubMed:17020768};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12054870, ECO:0000269|PubMed:15583379};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:12054870,
CC ECO:0000269|PubMed:15583379};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=410 uM for shikimate {ECO:0000269|PubMed:12054870};
CC KM=83 uM for ATP {ECO:0000269|PubMed:12054870};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis;
CC chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate: step
CC 5/7.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11483005,
CC ECO:0000269|PubMed:12054870, ECO:0000269|PubMed:15358538,
CC ECO:0000269|PubMed:15583379, ECO:0000269|PubMed:16834327,
CC ECO:0000269|PubMed:17020768, ECO:0000269|PubMed:17183161}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: Consists of three domains: the CORE domain which forms the
CC binding site for nucleotides, the LID domain which closes over the
CC active site upon ATP or shikimate binding, and the substrate-binding
CC domain which functions to recognize and bind shikimate.
CC -!- MISCELLANEOUS: The phosphoryl transfer proceeds by an in-line
CC associative mechanism. The random sequential binding of shikimate and
CC nucleotide is associated with domain movements that suggest a synergic
CC mechanism by which binding of the first substrate may enhance the
CC affinity for the second substrate. {ECO:0000269|PubMed:17020768}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the shikimate kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP45334.1; -; Genomic_DNA.
DR PIR; G70658; G70658.
DR RefSeq; NP_217055.1; NC_000962.3.
DR RefSeq; WP_003413021.1; NZ_NVQJ01000032.1.
DR PDB; 1L4U; X-ray; 1.80 A; A=1-176.
DR PDB; 1L4Y; X-ray; 2.00 A; A=1-176.
DR PDB; 1U8A; X-ray; 2.15 A; A=1-176.
DR PDB; 1WE2; X-ray; 2.30 A; A=1-176.
DR PDB; 1ZYU; X-ray; 2.90 A; A=1-176.
DR PDB; 2DFN; X-ray; 1.93 A; A=1-176.
DR PDB; 2DFT; X-ray; 2.80 A; A/B/C/D=1-176.
DR PDB; 2G1J; X-ray; 2.00 A; A/B=1-176.
DR PDB; 2G1K; X-ray; 1.75 A; A=1-176.
DR PDB; 2IYQ; X-ray; 1.80 A; A=1-176.
DR PDB; 2IYR; X-ray; 1.98 A; A/B=1-176.
DR PDB; 2IYS; X-ray; 1.40 A; A=1-176.
DR PDB; 2IYT; X-ray; 1.47 A; A=1-176.
DR PDB; 2IYU; X-ray; 1.85 A; A=1-176.
DR PDB; 2IYV; X-ray; 1.35 A; A=1-176.
DR PDB; 2IYW; X-ray; 1.85 A; A=1-176.
DR PDB; 2IYX; X-ray; 1.49 A; A=1-176.
DR PDB; 2IYY; X-ray; 1.62 A; A=1-176.
DR PDB; 2IYZ; X-ray; 2.30 A; A=1-176.
DR PDB; 3BAF; X-ray; 2.25 A; A=1-176.
DR PDB; 4BQS; X-ray; 2.15 A; A/B/C=1-176.
DR PDBsum; 1L4U; -.
DR PDBsum; 1L4Y; -.
DR PDBsum; 1U8A; -.
DR PDBsum; 1WE2; -.
DR PDBsum; 1ZYU; -.
DR PDBsum; 2DFN; -.
DR PDBsum; 2DFT; -.
DR PDBsum; 2G1J; -.
DR PDBsum; 2G1K; -.
DR PDBsum; 2IYQ; -.
DR PDBsum; 2IYR; -.
DR PDBsum; 2IYS; -.
DR PDBsum; 2IYT; -.
DR PDBsum; 2IYU; -.
DR PDBsum; 2IYV; -.
DR PDBsum; 2IYW; -.
DR PDBsum; 2IYX; -.
DR PDBsum; 2IYY; -.
DR PDBsum; 2IYZ; -.
DR PDBsum; 3BAF; -.
DR PDBsum; 4BQS; -.
DR AlphaFoldDB; P9WPY3; -.
DR SMR; P9WPY3; -.
DR STRING; 83332.Rv2539c; -.
DR PaxDb; P9WPY3; -.
DR DNASU; 887434; -.
DR GeneID; 887434; -.
DR KEGG; mtu:Rv2539c; -.
DR TubercuList; Rv2539c; -.
DR eggNOG; COG0703; Bacteria.
DR OMA; IGKHLFE; -.
DR PhylomeDB; P9WPY3; -.
DR BRENDA; 2.7.1.71; 3445.
DR Reactome; R-MTU-964903; Chorismate via Shikimate Pathway.
DR UniPathway; UPA00053; UER00088.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0004765; F:shikimate kinase activity; IDA:MTBBASE.
DR GO; GO:0009073; P:aromatic amino acid family biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009423; P:chorismate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0019632; P:shikimate metabolic process; IDA:MTBBASE.
DR CDD; cd00464; SK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00109; Shikimate_kinase; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR031322; Shikimate/glucono_kinase.
DR InterPro; IPR000623; Shikimate_kinase/TSH1.
DR InterPro; IPR023000; Shikimate_kinase_CS.
DR Pfam; PF01202; SKI; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS01128; SHIKIMATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Aromatic amino acid biosynthesis;
KW ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..176
FT /note="Shikimate kinase"
FT /id="PRO_0000192393"
FT REGION 112..124
FT /note="LID domain"
FT BINDING 12..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 16
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 34
FT /ligand="substrate"
FT BINDING 58
FT /ligand="substrate"
FT BINDING 80
FT /ligand="substrate"
FT BINDING 117
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 136
FT /ligand="substrate"
FT BINDING 153
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:2IYV"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 33..41
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 54..71
FT /evidence="ECO:0007829|PDB:2IYV"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:2IYV"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:2IYV"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:1L4U"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:2IYS"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:2IYX"
FT HELIX 125..143
FT /evidence="ECO:0007829|PDB:2IYV"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:2IYV"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 155..163
FT /evidence="ECO:0007829|PDB:2IYV"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:2IYV"
SQ SEQUENCE 176 AA; 18583 MW; 208EE0C38F5186A1 CRC64;
MAPKAVLVGL PGSGKSTIGR RLAKALGVGL LDTDVAIEQR TGRSIADIFA TDGEQEFRRI
EEDVVRAALA DHDGVLSLGG GAVTSPGVRA ALAGHTVVYL EISAAEGVRR TGGNTVRPLL
AGPDRAEKYR ALMAKRAPLY RRVATMRVDT NRRNPGAVVR HILSRLQVPS PSEAAT
