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| | <StructureSection load='6qya' size='340' side='right'caption='[[6qya]], [[Resolution|resolution]] 1.76Å' scene=''> | | <StructureSection load='6qya' size='340' side='right'caption='[[6qya]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qya]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QYA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QYA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qya]] 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=6QYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QYA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FOZ:N-[4-({[(6S)-2-AMINO-5-FORMYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC+ACID'>FOZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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]] 1.76Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</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>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6qxg|6qxg]], [[6qxh|6qxh]], [[6qxs|6qxs]]</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=6qya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qya OCA], [https://pdbe.org/6qya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qya RCSB], [https://www.ebi.ac.uk/pdbsum/6qya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qya ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qya OCA], [http://pdbe.org/6qya PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qya RCSB], [http://www.ebi.ac.uk/pdbsum/6qya PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qya 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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| | </div> | | </div> |
| | <div class="pdbe-citations 6qya" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6qya" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Enterococcus faecalis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymidylate synthase]]
| + | [[Category: Mangani M]] |
| - | [[Category: Mangani, M]] | + | [[Category: Pozzi C]] |
| - | [[Category: Pozzi, C]] | + | |
| - | [[Category: Dump]]
| + | |
| - | [[Category: Eft]]
| + | |
| - | [[Category: Enteroccocus faecalis thymidylate synthase]]
| + | |
| - | [[Category: Folate pathway]]
| + | |
| - | [[Category: Substrate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
6qya 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 1.76Å |
| Ligands: | , , , , , , |
| 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
Thymidylate synthase (TS) is an enzyme of paramount importance as it provides the only de novo source of deoxy-thymidine monophosphate (dTMP). dTMP, essential for DNA synthesis, is produced by the TS-catalyzed reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) using N(5),N(10)-methylenetetrahydrofolate (mTHF) as a cofactor. TS is ubiquitous and a validated drug target. TS enzymes from different organisms differ in sequence and structure, but are all obligate homodimers. The structural and mechanistic differences between the human and bacterial enzymes are exploitable to obtain selective inhibitors of bacterial TSs that can enrich the currently available therapeutic tools against bacterial infections. Enterococcus faecalis is a pathogen fully dependent on TS for dTMP synthesis. In this study, we present four new crystal structures of Enterococcus faecalis and human TSs in complex with either the substrate dUMP or the inhibitor FdUMP. The results provide new clues about the half-site reactivity of Enterococcus faecalis TS and the mechanisms underlying the conformational changes occurring in the two enzymes. We also identify relevant differences in cofactor and inhibitor binding between Enterococcus faecalis and human TS that can guide the design of selective inhibitors against bacterial TSs.
Structural Comparison of Enterococcus faecalis and Human Thymidylate Synthase Complexes with the Substrate dUMP and Its Analogue FdUMP Provides Hints about Enzyme Conformational Variabilities.,Pozzi C, Ferrari S, Luciani R, Tassone G, Costi MP, Mangani S Molecules. 2019 Mar 31;24(7). pii: molecules24071257. doi:, 10.3390/molecules24071257. PMID:30935102[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pozzi C, Ferrari S, Luciani R, Tassone G, Costi MP, Mangani S. Structural Comparison of Enterococcus faecalis and Human Thymidylate Synthase Complexes with the Substrate dUMP and Its Analogue FdUMP Provides Hints about Enzyme Conformational Variabilities. Molecules. 2019 Mar 31;24(7). pii: molecules24071257. doi:, 10.3390/molecules24071257. PMID:30935102 doi:http://dx.doi.org/10.3390/molecules24071257
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