View source for 3uwl


==Crystal structure of Enteroccocus faecalis thymidylate synthase (EfTS) in complex with 5-formyl tetrahydrofolate==
<StructureSection load='3uwl' size='340' side='right'caption='[[3uwl]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3uwl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UWL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.07&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FFO:N-[4-({[(6S)-2-AMINO-5-FORMYL-4-OXO-3,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC+ACID'>FFO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3uwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uwl OCA], [https://pdbe.org/3uwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uwl RCSB], [https://www.ebi.ac.uk/pdbsum/3uwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uwl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYSY_ENTFA TYSY_ENTFA] Provides the sole de novo source of dTMP for DNA biosynthesis.[HAMAP-Rule:MF_00008]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism.,Pozzi C, Ferrari S, Cortesi D, Luciani R, Stroud RM, Catalano A, Costi MP, Mangani S Acta Crystallogr D Biol Crystallogr. 2012 Sep;68(Pt 9):1232-41. doi:, 10.1107/S0907444912026236. Epub 2012 Aug 18. PMID:22948925<ref>PMID:22948925</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3uwl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus faecalis]]
[[Category: Large Structures]]
[[Category: Catalano A]]
[[Category: Cortesi D]]
[[Category: Costi MP]]
[[Category: Ferrari S]]
[[Category: Fritz T]]
[[Category: Luciani R]]
[[Category: Mangani S]]
[[Category: Pozzi C]]