Towards new thymidine phosphorylase/PD-ECGF inhibitors based on the transition state of the enzyme reaction.
Computational studies have been conducted to built a closed form of TPase and to characterize the transition state of the phosphorylisis reaction catalyzed by TPase. The results obtained point to a crucial role of His-85 and the O2 of thymine in the catalysis. This modelled transition state forms the basis for the design of new TPase inhibitors.
Priego
E M
EM
Instituto de Química Médica (C.S.I.C.), Madrid, Spain. empriego@iqm.csic.es
Mendieta
J
J
Gago
F
F
Balzarini
J
J
De Clercq
E
E
Camarasa
M J
MJ
Pérez-Pérez
M J
MJ
D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006639:Histidine; D007700:Kinetics; D011487:Protein Conformation; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013941:Thymine
D004791:Enzyme Inhibitors; D006639:Histidine; D013939:Thymidine Phosphorylase; D013941:Thymine