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Literature summary for 2.7.4.9 extracted from

  • Vanheusden, V.; Munier-Lehmann, H.; Froeyen, M.; Busson, R.; Rozenski, J.; Herdewijn, P.; Van Calenbergh, S.
    Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (2004), J. Med. Chem., 47, 6187-6194.
    View publication on PubMed
Search for more literature for 2.7.4.9

Application

Application Comment Organism
drug development potential target for the development of new antituberculosis drugs due to the low sequence similarity with the human enzyme Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Homo sapiens
expressed in Escherichia coli Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
1,3-bis[[(2S,3R,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]methyl]urea
-
 Homo sapiens
1,3-bis[[(2S,3R,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]methyl]urea
-
 Mycobacterium tuberculosis
1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-oxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Homo sapiens
1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-oxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Mycobacterium tuberculosis
1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-thioxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Homo sapiens
1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-thioxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Mycobacterium tuberculosis
2',5'-difluoro-3'-azidomethylthymidine
-
 Mycobacterium tuberculosis
2'-chlorothymidine 5'-monophosphate
-
 Mycobacterium tuberculosis
2'-fluorothymidine 5'-monophosphate
-
 Mycobacterium tuberculosis
3'-(aminomethyl)-2'-chloro-3'-deoxythymidine
-
 Mycobacterium tuberculosis
3'-(aminomethyl)-3'-deoxythymidine
-
 Homo sapiens
3'-(aminomethyl)-3'-deoxythymidine
-
 Mycobacterium tuberculosis
3'-(azidomethyl)-2'-chloro-3'-deoxythymidine
-
 Mycobacterium tuberculosis
3'-(azidomethyl)-3'-deoxy-2'-fluorothymidine
-
 Mycobacterium tuberculosis
3'-(azidomethyl)-3'-deoxy-alpha-D-ribosyl-thymine
-
 Homo sapiens
3'-(azidomethyl)-3'-deoxy-alpha-D-ribosyl-thymine
-
 Mycobacterium tuberculosis
3'-(azidomethyl)-3'-deoxythymidine
-
 Homo sapiens
3'-(azidomethyl)-3'-deoxythymidine
-
 Mycobacterium tuberculosis
3'-azido-3'-deoxythymidine
-
 Mycobacterium tuberculosis
3'-azido-3'-deoxythymidine 5'-monophosphate potential inhibitor of the bacterial enzyme, not inhibitory in human Mycobacterium tuberculosis
3'-azido-3'-deoxythymidine 5'-phosphate
-
 Mycobacterium tuberculosis
3'-deoxythymidine 5'-monophosphate
-
 Mycobacterium tuberculosis
dTMP
-
 Homo sapiens
dTMP
-
 Mycobacterium tuberculosis
additional information 3’-azido-3’-deoxythymidine monophosphate is not inhibitory, various thymine derivatives tested and found to inhibit activity to different extents Homo sapiens
additional information 3'-(aminomethyl)-3'-deoxy-2'-fluorothymidine is not inhibitory at 1 mM; 3’-azido-3’-deoxythymidine monophosphate is not inhibitory, various thymine derivatives tested and found to inhibit activity to different extents Mycobacterium tuberculosis
thymidine
-
 Homo sapiens
thymidine
-
 Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0045
-
 dTMP pH 7.4 Mycobacterium tuberculosis
0.005
-
 dTMP pH 7.4 Homo sapiens
0.012
-
 3'-azido-3'-deoxythymidine monophosphate pH 7.4 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ bound to enzyme, displacement of Mg2+ might be responsible for inhibitory effect of the enzyme inhibitors Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + dTMP Homo sapiens involved in dTTP metabolism, essential for cell proliferation ADP + dTDP
-
 ?
ATP + dTMP Mycobacterium tuberculosis involved in dTTP metabolism, essential for cell proliferation ADP + dTDP
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mycobacterium tuberculosis P9WKE1
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 3'-azido-3'-deoxythymidine monophosphate
-
 Homo sapiens ADP + 3'-azido-3'-deoxythymidine diphosphate
-
 ?
ATP + dTMP
-
 Homo sapiens ADP + dTDP
-
 ?
ATP + dTMP
-
 Mycobacterium tuberculosis ADP + dTDP
-
 ?
ATP + dTMP involved in dTTP metabolism, essential for cell proliferation Homo sapiens ADP + dTDP
-
 ?
ATP + dTMP involved in dTTP metabolism, essential for cell proliferation Mycobacterium tuberculosis ADP + dTDP
-
 ?

Synonyms

Synonyms Comment Organism
TMPK
-
 Homo sapiens
TMPK
-
 Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0035
-
 1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-thioxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Mycobacterium tuberculosis
0.0045
-
 dTMP
-
 Mycobacterium tuberculosis
0.005
-
 dTMP
-
 Homo sapiens
0.01
-
 3'-azido-3'-deoxythymidine 5'-phosphate pH 7.4 Mycobacterium tuberculosis
0.0135
-
 1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-oxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Mycobacterium tuberculosis
0.019
-
 2'-chlorothymidine 5'-monophosphate
-
 Mycobacterium tuberculosis
0.027
-
 thymidine
-
 Mycobacterium tuberculosis
0.029
-
 1,3-bis[[(2S,3R,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]methyl]urea
-
 Mycobacterium tuberculosis
0.04
-
 3'-(azidomethyl)-3'-deoxythymidine
-
 Mycobacterium tuberculosis
0.043
-
 2'-fluorothymidine 5'-monophosphate
-
 Mycobacterium tuberculosis
0.057
-
 3'-(aminomethyl)-3'-deoxythymidine
-
 Mycobacterium tuberculosis
0.08
-
 2',5'-difluoro-3'-azidomethylthymidine
-
 Mycobacterium tuberculosis
0.165
-
 3'-(azidomethyl)-3'-deoxy-2'-fluorothymidine
-
 Mycobacterium tuberculosis
0.18
-
 thymidine
-
 Homo sapiens
0.18
-
 3'-(azidomethyl)-2'-chloro-3'-deoxythymidine
-
 Mycobacterium tuberculosis
0.22
-
 3'-(aminomethyl)-3'-deoxythymidine
-
 Homo sapiens
0.39
-
 3'-(aminomethyl)-2'-chloro-3'-deoxythymidine
-
 Mycobacterium tuberculosis
0.7
-
 1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-thioxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Homo sapiens
1.04
-
 3'-(azidomethyl)-3'-deoxythymidine
-
 Homo sapiens
1.1
-
 1-[(4aR,5S,7R,7aR)-5-(hydroxymethyl)-2-oxohexahydro-2H-furo[3,4-e][1,3]oxazin-7-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
 Homo sapiens