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| | <StructureSection load='5j7w' size='340' side='right'caption='[[5j7w]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='5j7w' size='340' side='right'caption='[[5j7w]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5j7w]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J7W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J7W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5j7w]] 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=5J7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J7W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thyA, EF_1576 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></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=5j7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j7w OCA], [https://pdbe.org/5j7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j7w RCSB], [https://www.ebi.ac.uk/pdbsum/5j7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j7w ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5j7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j7w OCA], [http://pdbe.org/5j7w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j7w RCSB], [http://www.ebi.ac.uk/pdbsum/5j7w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j7w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYSY_ENTFA TYSY_ENTFA]] Provides the sole de novo source of dTMP for DNA biosynthesis.[HAMAP-Rule:MF_00008] | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | + | [[Category: Enterococcus faecalis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymidylate synthase]]
| + | [[Category: Mangani S]] |
| - | [[Category: Mangani, S]] | + | [[Category: Pozzi C]] |
| - | [[Category: Pozzi, C]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Enterococcus faecali]]
| + | |
| - | [[Category: Methotrexate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Catalano A, Luciani R, Carocci A, Cortesi D, Pozzi C, Borsari C, Ferrari S, Mangani S. X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors. Eur J Med Chem. 2016 Nov 10;123:649-64. doi: 10.1016/j.ejmech.2016.07.066. Epub, 2016 Jul 29. PMID:27517810 doi:http://dx.doi.org/10.1016/j.ejmech.2016.07.066
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