Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6088
Title: The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism.
Authors: Pozzi, Cecilia 
Ferrari, S
Cortesi, D
Luciani, R
Stroud, Rm
Catalano, A
Costi, Mp
Mangani, Stefano 
Keywords: x-ray; crystal structure; enterococcus faecalis; thymidylate synthase; folate
Issue Date: 2012
Project: None 
Journal: ACTA CRYSTALLOGRAPHICA. SECTION D
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.
Description: 
54623
URI: http://hdl.handle.net/20.500.12779/6088
ISSN: 1399-0047
DOI: 10.1107/S0907444912026236
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