5j7w

Enterococcus faecalis thymidylate synthase complex with methotrexate

spinqualitylabelsall models 5j7w, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5j7w is a 4 chain structure with sequence from Enterococcus faecalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: MTX, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TYSY_ENTFA Provides the sole de novo source of dTMP for DNA biosynthesis.[HAMAP-Rule:MF_00008] Publication Abstract from PubMed Infections caused by Enterococcus faecalis (Ef) represent nowadays a relevant health problem. We selected Thymidylate synthase (TS) from this organism as a potential specific target for antibacterial therapy. We have previously demonstrated that species-specific inhibition of the protein can be achieved despite the relatively high structural similarity among bacterial TSs and human TS. We had previously obtained the EfTS crystal structure of the protein in complex with the metabolite 5-formyl-tetrahydrofolate (5-FTHF) suggesting the protein role as metabolite reservoir; however, protein-inhibitors complexes were still missing. In the present work we identified some inhibitors bearing the phthalimidic core from our in-house library and we performed crystallographic screening towards EfTS. We obtained two X-ray crystallographic structures: the first with a weak phthalimidic inhibitor bound in one subunit and 5-hydroxymethylene-6-hydrofolic acid (5-HMHF) in the other subunit; a second X-ray structure complex with methotrexate. The structural information achieved confirm the role of EfTS as an enzyme involved in the folate pool system and provide a structural basis for structure-based drug design. X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors.,Catalano A, Luciani R, Carocci A, Cortesi D, Pozzi C, Borsari C, Ferrari S, Mangani S Eur J Med Chem. 2016 Nov 10;123:649-64. doi: 10.1016/j.ejmech.2016.07.066. Epub, 2016 Jul 29. PMID:27517810 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate synthase 3D structures

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