ADOK_MYCTU
ID ADOK_MYCTU Reviewed; 324 AA.
AC P9WID5; L0T8X3; P83734; Q10391;
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=Adenosine kinase {ECO:0000303|PubMed:14594827, ECO:0000303|PubMed:16511094};
DE Short=ADK {ECO:0000303|PubMed:17597075, ECO:0000303|PubMed:25259627};
DE Short=AK {ECO:0000303|PubMed:14594827, ECO:0000303|PubMed:16511094};
DE EC=2.7.1.20 {ECO:0000269|PubMed:14594827, ECO:0000269|PubMed:16511094};
GN Name=adoK {ECO:0000303|PubMed:14594827}; Synonyms=cbhK;
GN OrderedLocusNames=Rv2202c; ORFNames=MTCY190.13c;
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 [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 [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, SUBUNIT,
RP ACTIVITY REGULATION, AND PATHWAY.
RC STRAIN=H37Rv;
RX PubMed=14594827; DOI=10.1128/jb.185.22.6548-6555.2003;
RA Long M.C., Escuyer V., Parker W.B.;
RT "Identification and characterization of a unique adenosine kinase from
RT Mycobacterium tuberculosis.";
RL J. Bacteriol. 185:6548-6555(2003).
RN [3]
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 [4]
RP CRYSTALLIZATION, FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=16511094; DOI=10.1107/s1744309105013473;
RA Wang Y., Long M.C., Ranganathan S., Escuyer V., Parker W.B., Li R.;
RT "Overexpression, purification and crystallographic analysis of a unique
RT adenosine kinase from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 61:553-557(2005).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 (1.50 ANGSTROMS) OF APOENZYME AND IN COMPLEXES WITH
RP ADENOSINE; 2-FLUOROADENOSINE AND AN ATP ANALOG, SUBUNIT, PATHWAY, REACTION
RP MECHANISM, AND ACTIVE SITE.
RC STRAIN=H37Rv;
RX PubMed=17597075; DOI=10.1074/jbc.m703290200;
RA Reddy M.C., Palaninathan S.K., Shetty N.D., Owen J.L., Watson M.D.,
RA Sacchettini J.C.;
RT "High resolution crystal structures of Mycobacterium tuberculosis adenosine
RT kinase: insights into the mechanism and specificity of this novel
RT prokaryotic enzyme.";
RL J. Biol. Chem. 282:27334-27342(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEXES WITH ATP ANALOG AND
RP 7-ETHYNYL-7-DEAZAADENOSINE INHIBITOR, ACTIVITY REGULATION, AND INHIBITOR
RP SCREENING.
RX PubMed=25259627; DOI=10.1021/jm500497v;
RA Snasel J., Naus P., Dostal J., Hnizda A., Fanfrlik J., Brynda J.,
RA Bourderioux A., Dusek M., Dvorakova H., Stolarikova J., Zabranska H.,
RA Pohl R., Konecny P., Dzubak P., Votruba I., Hajduch M., Rezacova P.,
RA Veverka V., Hocek M., Pichova I.;
RT "Structural basis for inhibition of mycobacterial and human adenosine
RT kinase by 7-substituted 7-(het)aryl-7-deazaadenine ribonucleosides.";
RL J. Med. Chem. 57:8268-8279(2014).
CC -!- FUNCTION: Catalyzes the phosphorylation of adenosine to adenosine
CC monophosphate (AMP) (PubMed:14594827, PubMed:16511094). Can also
CC catalyze the phosphorylation of the adenosine analog 2-methyladenosine
CC (methyl-Ado) to methyl-AMP, the first step in the metabolism of this
CC compound to an active form that displays antitubercular activity. Is
CC not active on guanosine, inosine, deoxyadenosine, cytidine, uridine, or
CC thymidine. Prefers dGTP and GTP to ATP as phosphate donors in vitro
CC (PubMed:14594827). {ECO:0000269|PubMed:14594827,
CC ECO:0000269|PubMed:16511094}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + ATP = ADP + AMP + H(+); Xref=Rhea:RHEA:20824,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.1.20;
CC Evidence={ECO:0000269|PubMed:14594827, ECO:0000269|PubMed:16511094};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + GTP = AMP + GDP + H(+); Xref=Rhea:RHEA:52532,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:14594827};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + dGTP = AMP + dGDP + H(+); Xref=Rhea:RHEA:52536,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:58595,
CC ChEBI:CHEBI:61429, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:14594827};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14594827};
CC -!- ACTIVITY REGULATION: The enzyme is subject to substrate inhibition by
CC adenosine and is competitively inhibited by the adenosine analog
CC iodotubercidin. Unlike other adenosine kinases it is not stimulated by
CC inorganic phosphate. Activity is stimulated in the presence of
CC potassium (PubMed:14594827). Is inhibited by a series of 7-(het)aryl-7-
CC deazaadenine ribonucleosides bearing small and bulky substituents in
CC position 7; some of them display micromolar antimycobacterial activity
CC and low cytotoxicity (PubMed:25259627). {ECO:0000269|PubMed:14594827,
CC ECO:0000269|PubMed:25259627}.
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway; AMP
CC from adenosine: step 1/1. {ECO:0000305|PubMed:14594827,
CC ECO:0000305|PubMed:17597075}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14594827,
CC ECO:0000269|PubMed:16511094, ECO:0000269|PubMed:17597075}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44979.1; -; Genomic_DNA.
DR PIR; C70785; C70785.
DR RefSeq; NP_216718.1; NC_000962.3.
DR RefSeq; WP_003411414.1; NZ_NVQJ01000008.1.
DR PDB; 2PKF; X-ray; 1.50 A; A/B=1-324.
DR PDB; 2PKK; X-ray; 1.93 A; A=1-324.
DR PDB; 2PKM; X-ray; 1.90 A; A=1-324.
DR PDB; 2PKN; X-ray; 1.90 A; A=1-324.
DR PDB; 4O1G; X-ray; 1.50 A; A=1-324.
DR PDB; 4PVV; X-ray; 2.50 A; A=1-324.
DR PDB; 6C67; X-ray; 2.11 A; A/B=1-324.
DR PDB; 6C9N; X-ray; 2.10 A; A/B=1-324.
DR PDB; 6C9P; X-ray; 2.00 A; A/B=1-324.
DR PDB; 6C9Q; X-ray; 1.95 A; A=1-324.
DR PDB; 6C9R; X-ray; 2.10 A; A/B=1-324.
DR PDB; 6C9S; X-ray; 2.23 A; A/B=1-324.
DR PDB; 6C9V; X-ray; 1.70 A; A/B=1-324.
DR PDBsum; 2PKF; -.
DR PDBsum; 2PKK; -.
DR PDBsum; 2PKM; -.
DR PDBsum; 2PKN; -.
DR PDBsum; 4O1G; -.
DR PDBsum; 4PVV; -.
DR PDBsum; 6C67; -.
DR PDBsum; 6C9N; -.
DR PDBsum; 6C9P; -.
DR PDBsum; 6C9Q; -.
DR PDBsum; 6C9R; -.
DR PDBsum; 6C9S; -.
DR PDBsum; 6C9V; -.
DR AlphaFoldDB; P9WID5; -.
DR SMR; P9WID5; -.
DR STRING; 83332.Rv2202c; -.
DR BindingDB; P9WID5; -.
DR ChEMBL; CHEMBL4523271; -.
DR iPTMnet; P9WID5; -.
DR PaxDb; P9WID5; -.
DR DNASU; 888551; -.
DR GeneID; 45426178; -.
DR GeneID; 888551; -.
DR KEGG; mtu:Rv2202c; -.
DR TubercuList; Rv2202c; -.
DR eggNOG; COG0524; Bacteria.
DR OMA; SQQIARM; -.
DR PhylomeDB; P9WID5; -.
DR BRENDA; 2.7.1.20; 3445.
DR UniPathway; UPA00588; UER00659.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004001; F:adenosine kinase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0032567; F:dGTP binding; IDA:MTBBASE.
DR GO; GO:0005525; F:GTP binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0044209; P:AMP salvage; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR Gene3D; 3.40.1190.20; -; 1.
DR InterPro; IPR002173; Carboh/pur_kinase_PfkB_CS.
DR InterPro; IPR011611; PfkB_dom.
DR InterPro; IPR029056; Ribokinase-like.
DR Pfam; PF00294; PfkB; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
DR PROSITE; PS00583; PFKB_KINASES_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Kinase; Magnesium;
KW Nucleotide-binding; Purine salvage; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..324
FT /note="Adenosine kinase"
FT /id="PRO_0000080064"
FT ACT_SITE 257
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:17597075"
FT BINDING 8
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 12
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 36
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 48
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 52
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 102
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 116
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 172..173
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT BINDING 195
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0000305|PubMed:25259627, ECO:0007744|PDB:4O1G"
FT BINDING 223..228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0000305|PubMed:25259627, ECO:0007744|PDB:2PKN,
FT ECO:0007744|PDB:4O1G"
FT BINDING 256
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:25259627,
FT ECO:0007744|PDB:4O1G"
FT BINDING 257
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:17597075,
FT ECO:0007744|PDB:2PKM"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 10..16
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:6C9V"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 49..59
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:2PKF"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4PVV"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 149..162
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 171..175
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 179..183
FT /evidence="ECO:0007829|PDB:2PKF"
FT TURN 184..188
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 196..206
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 210..214
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 255..268
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 273..288
FT /evidence="ECO:0007829|PDB:2PKF"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 300..311
FT /evidence="ECO:0007829|PDB:2PKF"
FT HELIX 313..320
FT /evidence="ECO:0007829|PDB:2PKF"
SQ SEQUENCE 324 AA; 34472 MW; 0C072206A3210A1D CRC64;
MTIAVTGSIA TDHLMRFPGR FSEQLLPEHL HKVSLSFLVD DLVMHRGGVA GNMAFAIGVL
GGEVALVGAA GADFADYRDW LKARGVNCDH VLISETAHTA RFTCTTDVDM AQIASFYPGA
MSEARNIKLA DVVSAIGKPE LVIIGANDPE AMFLHTEECR KLGLAFAADP SQQLARLSGE
EIRRLVNGAA YLFTNDYEWD LLLSKTGWSE ADVMAQIDLR VTTLGPKGVD LVEPDGTTIH
VGVVPETSQT DPTGVGDAFR AGFLTGRSAG LGLERSAQLG SLVAVLVLES TGTQEWQWDY
EAAASRLAGA YGEHAAAEIV AVLA
