1uou
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1uou |SIZE=350|CAPTION= <scene name='initialview01'>1uou</scene>, resolution 2.11Å | |PDB= 1uou |SIZE=350|CAPTION= <scene name='initialview01'>1uou</scene>, resolution 2.11Å | ||
|SITE= <scene name='pdbsite=AC1:Cmu+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Cmu+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=CMU:5-CHLORO-6-(1-(2-IMINOPYRROLIDINYL) METHYL) URACIL'>CMU</scene> | + | |LIGAND= <scene name='pdbligand=CMU:5-CHLORO-6-(1-(2-IMINOPYRROLIDINYL)+METHYL)+URACIL'>CMU</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Thymidine_phosphorylase Thymidine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.4 2.4.2.4] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidine_phosphorylase Thymidine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.4 2.4.2.4] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uou OCA], [http://www.ebi.ac.uk/pdbsum/1uou PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uou RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy. | Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Mitochondrial neurogastrointestinal encephalomyopathy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131222 131222]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 41: | Line 41: | ||
[[Category: Timms, D.]] | [[Category: Timms, D.]] | ||
[[Category: Tucker, J A.]] | [[Category: Tucker, J A.]] | ||
| - | [[Category: CMU]] | ||
[[Category: angiogenesis]] | [[Category: angiogenesis]] | ||
[[Category: chemotaxis]] | [[Category: chemotaxis]] | ||
| Line 48: | Line 47: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:13:14 2008'' |
Revision as of 21:13, 30 March 2008
| |||||||
| , resolution 2.11Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Thymidine phosphorylase, with EC number 2.4.2.4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HUMAN THYMIDINE PHOSPHORYLASE IN COMPLEX WITH A SMALL MOLECULE INHIBITOR
Overview
Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy.
About this Structure
1UOU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor., Norman RA, Barry ST, Bate M, Breed J, Colls JG, Ernill RJ, Luke RW, Minshull CA, McAlister MS, McCall EJ, McMiken HH, Paterson DS, Timms D, Tucker JA, Pauptit RA, Structure. 2004 Jan;12(1):75-84. PMID:14725767
Page seeded by OCA on Mon Mar 31 00:13:14 2008
Categories: Homo sapiens | Single protein | Thymidine phosphorylase | Barry, S T. | Bate, M. | Breed, J. | Colls, J G. | Ernill, R J. | Luke, R W.A. | Mcalister, M S.B. | Mccall, E J. | Mcmiken, H H.J. | Minshull, C A. | Norman, R A. | Paterson, D S. | Pauptit, R A. | Timms, D. | Tucker, J A. | Angiogenesis | Chemotaxis | Glycosyltransferase | Phosphorylase | Transferase
