Towards new thymidine phosphorylase/PD-ECGF inhibitors based on the transition state of the enzyme reaction

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):951-3. doi: 10.1081/NCN-120022693.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Histidine
  • Kinetics
  • Protein Conformation
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Thymidine Phosphorylase / chemistry*
  • Thymine

Substances

  • Enzyme Inhibitors
  • Histidine
  • Thymidine Phosphorylase
  • Thymine