| Structural highlights
4e28 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | |
| Related: | 3egy, 3ehi |
| Gene: | TYMS, TS, OK/SW-cl.29 (HUMAN) |
| Activity: | Thymidylate synthase, with EC number 2.1.1.45 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1]
Publication Abstract from PubMed
Human thymidylate synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxybenzylidene)hydrazono]-2,5-dihydrothiazol-5-yl}-N-(3-tr ifluoromethylphenyl)acetamide (5), showed a mixed-type inhibition pattern, with a K(i) of 1.3 muM and activity against ovarian cancer cell lines with the same potency as cisplatin. X-ray studies revealed that it binds the inactive enzyme conformation. This study is the first example of a nonpeptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.
Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase.,Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP J Med Chem. 2012 Nov 5. PMID:23075414[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi:, 10.1073/pnas.1103623108. Epub 2011 Aug 26. PMID:21876188 doi:10.1073/pnas.1103623108
- ↑ Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP. Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase. J Med Chem. 2012 Nov 5. PMID:23075414 doi:http://dx.doi.org/10.1021/jm300850v
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