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

被引：39
|
作者：
Mitsiki, Eirini [1 ]
Papageorgiou, Anastassios C. [1 ]
Iyer, Shalini [1 ]
Thiyagarajan, Nethaji [1 ]
Prior, Steven H. [1 ]
Sleep, Darrell [2 ]
Finnis, Chris [2 ]
Acharya, K. Ravi [1 ]
机构：
[1] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England
[2] Novozymes Biopharma UK Ltd, Nottingham NG7 1FD, England
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 386卷 / 04期
基金：
英国惠康基金;
关键词：
Thymidine phosphorylase; Crystal structure; Enzyme kinetics; Mutagenesis; 5-Iodouracil; CELL GROWTH-FACTOR; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; TUMOR-GROWTH; INHIBITION; PROGRAM; DESIGN; PLOTS;
D O I：
10.1016/j.bbrc.2009.06.104
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：666 / 670
页数：5
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