ADOK_MYCTA
ID ADOK_MYCTA Reviewed; 324 AA.
AC A5U4N0;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Adenosine kinase {ECO:0000303|PubMed:14594827};
DE Short=ADK {ECO:0000250|UniProtKB:P9WID5};
DE Short=AK {ECO:0000303|PubMed:14594827};
DE EC=2.7.1.20 {ECO:0000269|PubMed:14594827};
GN Name=adoK {ECO:0000303|PubMed:14594827}; Synonyms=cbhK;
GN OrderedLocusNames=MRA_2218;
OS Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=419947;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25177 / H37Ra;
RX PubMed=18584054; DOI=10.1371/journal.pone.0002375;
RA Zheng H., Lu L., Wang B., Pu S., Zhang X., Zhu G., Shi W., Zhang L.,
RA Wang H., Wang S., Zhao G., Zhang Y.;
RT "Genetic basis of virulence attenuation revealed by comparative genomic
RT analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.";
RL PLoS ONE 3:E2375-E2375(2008).
RN [2]
RP PROTEIN SEQUENCE OF 2-16, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBUNIT, ACTIVITY
RP REGULATION, AND PATHWAY.
RC STRAIN=ATCC 25177 / H37Ra;
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).
CC -!- FUNCTION: Catalyzes the phosphorylation of adenosine to adenosine
CC monophosphate (AMP). Can also catalyze the phosphorylation of the
CC adenosine analog 2-methyladenosine (methyl-Ado) to methyl-AMP, the
CC first step in the metabolism of this compound to an active form that
CC displays antitubercular activity. Is not active on guanosine, inosine,
CC deoxyadenosine, cytidine, uridine, or thymidine. Prefers dGTP and GTP
CC to ATP as phosphate donors in vitro. {ECO:0000269|PubMed:14594827}.
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};
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, resulting in a 13- and 300-fold increase in the catalytic
CC efficiency with adenosine and methyl-Ado as substrate, respectively;
CC the stimulatory effects are not observed in the presence of NaCl or
CC LiCl. {ECO:0000269|PubMed:14594827}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.80 uM for adenosine (in the presence of 10 mM KCl)
CC {ECO:0000269|PubMed:14594827};
CC KM=3.4 uM for adenosine (in the absence of KCl)
CC {ECO:0000269|PubMed:14594827};
CC KM=79 uM for methyl-adenosine (in the presence of 10 mM KCl)
CC {ECO:0000269|PubMed:14594827};
CC KM=709 uM for methyl-adenosine (in the absence of KCl)
CC {ECO:0000269|PubMed:14594827};
CC KM=1100 uM for ATP (in the presence of 10 mM KCl)
CC {ECO:0000269|PubMed:14594827};
CC Vmax=180 nmol/min/mg enzyme with adenosine as substrate (in the
CC presence of 10 mM KCl) {ECO:0000269|PubMed:14594827};
CC Vmax=60 nmol/min/mg enzyme with adenosine as substrate (in the
CC absence of KCl) {ECO:0000269|PubMed:14594827};
CC Vmax=72 nmol/min/mg enzyme with methyl-adenosine as substrate (in the
CC presence of 10 mM KCl) {ECO:0000269|PubMed:14594827};
CC Vmax=2.3 nmol/min/mg enzyme with methyl-adenosine as substrate (in
CC the absence of KCl) {ECO:0000269|PubMed:14594827};
CC Note=GTP and dGTP are the best phosphate donors, with 2.5 and 4.7
CC times the activity observed with ATP, respectively. UTP, dATP, and
CC dTTP exhibit about 33% of the activity observed with ATP, while CTP
CC and dCTP are the worst phosphate donors, with 1.7 and 0.2% of the
CC activity observed with ATP, respectively. Since K(+) exists at
CC millimolar levels within cells, stimulation by K(+) is
CC physiologically relevant, and kinetic values obtained in the presence
CC of K(+) more closely reflect the true physiological state of the
CC enzyme than values obtained in the absence of K(+).
CC {ECO:0000269|PubMed:14594827};
CC pH dependence:
CC Optimum pH is 8-11. Activity decreases rapidly at values above pH 11
CC and below pH 8. Is inactive at pH 4.3. {ECO:0000269|PubMed:14594827};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway; AMP
CC from adenosine: step 1/1. {ECO:0000305|PubMed:14594827}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14594827}.
CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family.
CC {ECO:0000305}.
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DR EMBL; CP000611; ABQ73980.1; -; Genomic_DNA.
DR RefSeq; WP_003411414.1; NZ_CP016972.1.
DR AlphaFoldDB; A5U4N0; -.
DR SMR; A5U4N0; -.
DR STRING; 419947.MRA_2218; -.
DR ChEMBL; CHEMBL4523106; -.
DR EnsemblBacteria; ABQ73980; ABQ73980; MRA_2218.
DR GeneID; 45426178; -.
DR KEGG; mra:MRA_2218; -.
DR eggNOG; COG0524; Bacteria.
DR HOGENOM; CLU_027634_5_2_11; -.
DR OMA; SQQIARM; -.
DR OrthoDB; 1604782at2; -.
DR BRENDA; 2.7.1.20; 3445.
DR SABIO-RK; A5U4N0; -.
DR UniPathway; UPA00588; UER00659.
DR Proteomes; UP000001988; Chromosome.
DR GO; GO:0004001; F:adenosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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 ATP-binding; Direct protein sequencing; Kinase; Magnesium;
KW Nucleotide-binding; Purine salvage; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:14594827"
FT CHAIN 2..324
FT /note="Adenosine kinase"
FT /id="PRO_0000306417"
FT ACT_SITE 257
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 8
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 12
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 36
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 48
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 52
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 102
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 116
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 172..173
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 195
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 223..228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 256
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
FT BINDING 257
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P9WID5"
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
