3hb8
From Proteopedia
(Difference between revisions)
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| - | + | ==Structures of Thymidylate Synthase R163K with Substrates and Inhibitors Show Subunit Asymmetry== | |
| - | + | <StructureSection load='3hb8' size='340' side='right' caption='[[3hb8]], [[Resolution|resolution]] 2.74Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3hb8]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HB8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HB8 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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">[[2rd8|2rd8]], [[2rda|2rda]], [[1hvy|1hvy]], [[1hw3|1hw3]], [[3h9k|3h9k]], [[3ob7|3ob7]]</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 Homo sapiens])</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=3hb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hb8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hb8 RCSB], [http://www.ebi.ac.uk/pdbsum/3hb8 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hb/3hb8_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:21206062</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
==See Also== | ==See Also== | ||
*[[Thymidylate synthase|Thymidylate synthase]] | *[[Thymidylate synthase|Thymidylate synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
| - | [[Category: Gibson, L M | + | [[Category: Gibson, L M]] |
[[Category: Lebioda, L]] | [[Category: Lebioda, L]] | ||
| - | [[Category: Lovelace, L L | + | [[Category: Lovelace, L L]] |
[[Category: Methyl transferase]] | [[Category: Methyl transferase]] | ||
[[Category: Methyltransferase]] | [[Category: Methyltransferase]] | ||
[[Category: Nucleotide biosynthesis]] | [[Category: Nucleotide biosynthesis]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 17:33, 18 December 2014
Structures of Thymidylate Synthase R163K with Substrates and Inhibitors Show Subunit Asymmetry
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