Structures of native human thymidine phosphorylase and in complex with 5-iodouracil

Biochem Biophys Res Commun. 2009 Sep 4;386(4):666-70. doi: 10.1016/j.bbrc.2009.06.104. Epub 2009 Jun 23.

Abstract

Thymidine phosphorylase (TP) first identified as platelet derived endothelial cell growth factor (PD-ECGF) plays a key role in nucleoside metabolism. Human TP (hTP) is implicated in angiogenesis and is overexpressed in several solid tumors. Here, we report the crystal structures of recombinant hTP and its complex with a substrate 5-iodouracil (5IUR) at 3.0 and 2.5A, respectively. In addition, we provide information on the role of specific residues in the enzymatic activity of hTP through mutagenesis and kinetic studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Mutation
  • Phosphates / chemistry
  • Protein Conformation
  • Thymidine Phosphorylase / chemistry*
  • Thymidine Phosphorylase / genetics
  • Uracil / analogs & derivatives*
  • Uracil / chemistry

Substances

  • Phosphates
  • Uracil
  • Thymidine Phosphorylase
  • 5-iodouracil