3UWL
Crystal structure of Enteroccocus faecalis thymidylate synthase (EfTS) in complex with 5-formyl tetrahydrofolate
Summary for 3UWL
| Entry DOI | 10.2210/pdb3uwl/pdb |
| Descriptor | Thymidylate synthase, SULFATE ION, N-[4-({[(6S)-2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid, ... (6 entities in total) |
| Functional Keywords | methyltransferase, transferase |
| Biological source | Enterococcus faecalis More |
| Total number of polymer chains | 4 |
| Total formula weight | 147715.94 |
| Authors | Pozzi, C.,Catalano, A.,Cortesi, D.,Luciani, R.,Ferrari, S.,Fritz, T.,Costi, M.P.,Mangani, S. (deposition date: 2011-12-02, release date: 2012-08-29, Last modification date: 2024-10-30) |
| Primary citation | Pozzi, C.,Ferrari, S.,Cortesi, D.,Luciani, R.,Stroud, R.M.,Catalano, A.,Costi, M.P.,Mangani, S. The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism. Acta Crystallogr.,Sect.D, 68:1232-1241, 2012 Cited by PubMed Abstract: Drug resistance to therapeutic antibiotics poses a challenge to the identification of novel targets and drugs for the treatment of infectious diseases. Infections caused by Enterococcus faecalis are a major health problem. Thymidylate synthase (TS) from E. faecalis is a potential target for antibacterial therapy. The X-ray crystallographic structure of E. faecalis thymidylate synthase (EfTS), which was obtained as a native binary complex composed of EfTS and 5-formyltetrahydrofolate (5-FTHF), has been determined. The structure provides evidence that EfTS is a half-of-the-sites reactive enzyme, as 5-FTHF is bound to two of the four independent subunits present in the crystal asymmetric unit. 5-FTHF is a metabolite of the one-carbon transfer reaction catalysed by 5-formyltetrahydrofolate cyclo-ligase. Kinetic studies show that 5-FTHF is a weak inhibitor of EfTS, suggesting that the EfTS-5-FTHF complex may function as a source of folates and/or may regulate one-carbon metabolism. The structure represents the first example of endogenous 5-FTHF bound to a protein involved in folate metabolism. PubMed: 22948925DOI: 10.1107/S0907444912026236 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.07 Å) |
Structure validation
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