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Literature summary for 2.4.2.4 extracted from

  • Bronckaers, A.; Aguado, L.; Negri, A.; Camarasa, M.J.; Balzarini, J.; Perez-Perez, M.J.; Gago, F.; Liekens, S.
    Identification of aspartic acid-203 in human thymidine phosphorylase as an important residue for both catalysis and non-competitive inhibition by the small molecule crystallization chaperone 5'-O-tritylinosine (KIN59) (2009), Biochem. Pharmacol., 78, 231-240.
    View publication on PubMed

Application

Application Comment Organism
medicine use of thymidine phosphorylase inhibitors might offer a promising strategy for cancer treatment Homo sapiens

Protein Variants

Protein Variants Comment Organism
D203A site-directed mutagenesis, the mutant enzyme shows 50fold reduced catalytic efficiency compared to the wild-type enzyme, the mutant also shows pronounced resistance to the inhibitory effect of 5'-O-tritylinosine, and it keeps full sensitivity to the competitive inhibitors 6-aminothymine and 6-amino-5-bromouracil Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
5'-O-tritylinosine i.e. KIN59, noncompetitive. Inhibitor docking and conformational changes, molecular modeling using the crystal structure of the enzyme, molecular dynamics simulations, binding site and mode, overview Homo sapiens
6-amino-5-bromouracil
-
Homo sapiens
6-aminothymine
-
Homo sapiens
7-deazaxanthine
-
Homo sapiens
9-[8-phosphonooctyl]-7-deazaxanthine
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.414
-
thymine pH 7.6, wild-type enzyme Homo sapiens
9.828
-
thymine pH 7.6, mutant D203A Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
thymidine + phosphate Homo sapiens
-
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P19971
-
-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell the enzyme is upregulated in many solid tumors Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
thymidine + phosphate
-
Homo sapiens thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
r
thymidine + phosphate Asp203 plays an important role to afford the substrate-binding site loop stabilization that is required for efficient enzyme catalysis Homo sapiens thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
r

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.6
-
assay at Homo sapiens

General Information

General Information Comment Organism
metabolism thymidine phosphorylase is a catabolic enzyme in thymidine metabolism Homo sapiens
additional information elevated enzyme levels are associated with tumor angiogenesis, metastasis and poor prognosis Homo sapiens