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 2.5 angstrom, respectively. in addition, we provide information on the role of specific residues in the enzymatic activity of hTP through mutagenesis and kinetic Studies. (C) 2009 Elsevier Inc. All rights reserved.