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 a...

Descripción completa

Detalles Bibliográficos
Autores principales: Mitsiki, Eirini, Papageorgiou, Anastassios C., Iyer, Shalini, Thiyagarajan, Nethaji, Prior, Steven H., Sleep, Darrell, Finnis, Chris, Acharya, K. Ravi
Formato: Texto
Lenguaje:English
Publicado: Academic Press 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719695/
https://www.ncbi.nlm.nih.gov/pubmed/19555658
http://dx.doi.org/10.1016/j.bbrc.2009.06.104
_version_ 1782170093041483776
author Mitsiki, Eirini
Papageorgiou, Anastassios C.
Iyer, Shalini
Thiyagarajan, Nethaji
Prior, Steven H.
Sleep, Darrell
Finnis, Chris
Acharya, K. Ravi
author_facet Mitsiki, Eirini
Papageorgiou, Anastassios C.
Iyer, Shalini
Thiyagarajan, Nethaji
Prior, Steven H.
Sleep, Darrell
Finnis, Chris
Acharya, K. Ravi
author_sort Mitsiki, Eirini
collection PubMed
description 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 Å, respectively. In addition, we provide information on the role of specific residues in the enzymatic activity of hTP through mutagenesis and kinetic studies.
format Text
id pubmed-2719695
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Academic Press
record_format MEDLINE/PubMed
spelling pubmed-27196952009-08-18 Structures of native human thymidine phosphorylase and in complex with 5-iodouracil Mitsiki, Eirini Papageorgiou, Anastassios C. Iyer, Shalini Thiyagarajan, Nethaji Prior, Steven H. Sleep, Darrell Finnis, Chris Acharya, K. Ravi Biochem Biophys Res Commun Article 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 Å, respectively. In addition, we provide information on the role of specific residues in the enzymatic activity of hTP through mutagenesis and kinetic studies. Academic Press 2009-09-04 /pmc/articles/PMC2719695/ /pubmed/19555658 http://dx.doi.org/10.1016/j.bbrc.2009.06.104 Text en © 2009 Elsevier Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Mitsiki, Eirini
Papageorgiou, Anastassios C.
Iyer, Shalini
Thiyagarajan, Nethaji
Prior, Steven H.
Sleep, Darrell
Finnis, Chris
Acharya, K. Ravi
Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title_full Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title_fullStr Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title_full_unstemmed Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title_short Structures of native human thymidine phosphorylase and in complex with 5-iodouracil
title_sort structures of native human thymidine phosphorylase and in complex with 5-iodouracil
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719695/
https://www.ncbi.nlm.nih.gov/pubmed/19555658
http://dx.doi.org/10.1016/j.bbrc.2009.06.104
work_keys_str_mv AT mitsikieirini structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT papageorgiouanastassiosc structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT iyershalini structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT thiyagarajannethaji structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT priorstevenh structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT sleepdarrell structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT finnischris structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil
AT acharyakravi structuresofnativehumanthymidinephosphorylaseandincomplexwith5iodouracil

Ejemplares similares