| Structural highlights
2wk5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 2j0f, 1uou, 2wk6 |
| Activity: | Thymidine phosphorylase, with EC number 2.4.2.4 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[TYPH_HUMAN] Mitochondrial neurogastrointestinal encephalomyopathy. The disease is caused by mutations affecting the gene represented in this entry.[1] [2]
Function
[TYPH_HUMAN] May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.[3] Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structures of native human thymidine phosphorylase and in complex with 5-iodouracil.,Mitsiki E, Papageorgiou AC, Iyer S, Thiyagarajan N, Prior SH, Sleep D, Finnis C, Acharya KR Biochem Biophys Res Commun. 2009 Sep 4;386(4):666-70. Epub 2009 Jun 23. PMID:19555658[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999 Jan 29;283(5402):689-92. PMID:9924029
- ↑ Gamez J, Ferreiro C, Accarino ML, Guarner L, Tadesse S, Marti RA, Andreu AL, Raguer N, Cervera C, Hirano M. Phenotypic variability in a Spanish family with MNGIE. Neurology. 2002 Aug 13;59(3):455-7. PMID:12177387
- ↑ Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A, Heldin CH. Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun. 1992 May 15;184(3):1311-6. PMID:1590793
- ↑ Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A, Heldin CH. Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun. 1992 May 15;184(3):1311-6. PMID:1590793
- ↑ Mitsiki E, Papageorgiou AC, Iyer S, Thiyagarajan N, Prior SH, Sleep D, Finnis C, Acharya KR. Structures of native human thymidine phosphorylase and in complex with 5-iodouracil. Biochem Biophys Res Commun. 2009 Sep 4;386(4):666-70. Epub 2009 Jun 23. PMID:19555658 doi:10.1016/j.bbrc.2009.06.104
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