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| | ==Human Thymidylate Synthase R163K with Cys 195 covalently modified by Glutathione== | | ==Human Thymidylate Synthase R163K with Cys 195 covalently modified by Glutathione== |
| - | <StructureSection load='3ob7' size='340' side='right' caption='[[3ob7]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='3ob7' size='340' side='right'caption='[[3ob7]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ob7]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ob7]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OB7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hb8|3hb8]], [[3h9k|3h9k]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ob7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob7 OCA], [https://pdbe.org/3ob7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ob7 RCSB], [https://www.ebi.ac.uk/pdbsum/3ob7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ob7 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=3ob7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob7 OCA], [http://pdbe.org/3ob7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ob7 RCSB], [http://www.ebi.ac.uk/pdbsum/3ob7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ob7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref> | + | [https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref> |
| | <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 3ob7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3ob7" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Thymidylate synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Celeste, L R]] | + | [[Category: Celeste LR]] |
| - | [[Category: Gibson, L M]] | + | [[Category: Gibson LM]] |
| - | [[Category: Lebioda, L]] | + | [[Category: Lebioda L]] |
| - | [[Category: Lovelace, L L]] | + | [[Category: Lovelace LL]] |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1]
Publication Abstract from PubMed
Thymidylate synthase (TS) is a well validated target in cancer chemotherapy. Here, a new crystal form of the R163K variant of human TS (hTS) with five subunits per asymmetric part of the unit cell, all with loop 181-197 in the active conformation, is reported. This form allows binding studies by soaking crystals in artificial mother liquors containing ligands that bind in the active site. Using this approach, crystal structures of hTS complexes with FdUMP and dUMP were obtained, indicating that this form should facilitate high-throughput analysis of hTS complexes with drug candidates. Crystal soaking experiments using oxidized glutathione revealed that hTS binds this ligand. Interestingly, the two types of binding observed are both asymmetric. In one subunit of the physiological dimer covalent modification of the catalytic nucleophile Cys195 takes place, while in another dimer a noncovalent adduct with reduced glutathione is formed in one of the active sites.
Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding.,Gibson LM, Celeste LR, Lovelace LL, Lebioda L Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):60-6. Epub 2010 Dec 16. PMID:21206062[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi:, 10.1073/pnas.1103623108. Epub 2011 Aug 26. PMID:21876188 doi:10.1073/pnas.1103623108
- ↑ Gibson LM, Celeste LR, Lovelace LL, Lebioda L. Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding. Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):60-6. Epub 2010 Dec 16. PMID:21206062 doi:10.1107/S0907444910044732
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