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| | <StructureSection load='3h9k' size='340' side='right'caption='[[3h9k]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='3h9k' size='340' side='right'caption='[[3h9k]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3h9k]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H9K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3h9k]] 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=3H9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H9K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</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]] 2.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rd8|2rd8]], [[2rda|2rda]], [[1hvy|1hvy]], [[1hw3|1hw3]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://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=3h9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h9k OCA], [https://pdbe.org/3h9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h9k RCSB], [https://www.ebi.ac.uk/pdbsum/3h9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h9k ProSAT]</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=3h9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h9k OCA], [https://pdbe.org/3h9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h9k RCSB], [https://www.ebi.ac.uk/pdbsum/3h9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h9k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymidylate synthase]]
| + | [[Category: Gibson LM]] |
| - | [[Category: Gibson, L M]] | + | [[Category: Lebioda L]] |
| - | [[Category: Lebioda, L]] | + | [[Category: Lovelace LL]] |
| - | [[Category: Lovelace, L L]] | + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Nucleotide biosynthesis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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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