Structures of native human thymidine phosphorylase and in complex with 5-iodouracil.
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.
Mitsiki
Eirini
E
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Papageorgiou
Anastassios C
AC
Iyer
Shalini
S
Thiyagarajan
Nethaji
N
Prior
Steven H
SH
Sleep
Darrell
D
Finnis
Chris
C
Acharya
K Ravi
KR
D018360:Crystallography, X-Ray; D006801:Humans; D009154:Mutation; D010710:Phosphates / Q000737:chemistry; D011487:Protein Conformation; D013939:Thymidine Phosphorylase / Q000737:chemistry* / Q000235:genetics; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
D010710:Phosphates; D014498:Uracil; D013939:Thymidine Phosphorylase; C048747:5-iodouracil