4e28

Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor

spinqualitylabelsall models 4e28, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4e28 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.302Å Ligands: 0MZ, 9MZ, CME, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate synthase 3D structures

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