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| | <StructureSection load='4psg' size='340' side='right'caption='[[4psg]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='4psg' size='340' side='right'caption='[[4psg]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4psg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PSG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PSG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4psg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PSG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOH:2-DEOXY-N-HYDROXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>NOH</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOH:2-DEOXY-N-HYDROXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>NOH</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4iqb|4iqb]], [[4irr|4irr]], [[4iqq|4iqq]], [[4g9u|4g9u]], [[4ein|4ein]], [[4ez8|4ez8]]</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=4psg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psg OCA], [https://pdbe.org/4psg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4psg RCSB], [https://www.ebi.ac.uk/pdbsum/4psg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4psg 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=4psg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psg OCA], [http://pdbe.org/4psg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4psg RCSB], [http://www.ebi.ac.uk/pdbsum/4psg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4psg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q9Y052_CAEEL Q9Y052_CAEEL] |
| - | The crystal structure of mouse thymidylate synthase (mTS) in complex with substrate dUMP and antifolate inhibitor Raltitrexed is reported. The structure reveals, for the first time in the group of mammalian TS structures, a well-ordered segment of 13 N-terminal amino acids, whose ordered conformation is stabilized due to specific crystal packing. The structure consists of two homodimers, differing in conformation, one being more closed (dimer AB) and thus supporting tighter binding of ligands, and the other being more open (dimer CD) and thus allowing weaker binding of ligands. This difference indicates an asymmetrical effect of the binding of Raltitrexed to two independent mTS molecules. Conformational changes leading to a ligand-induced closing of the active site cleft are observed by comparing the crystal structures of mTS in three different states along the catalytic pathway: ligand-free, dUMP-bound, and dUMP- and Raltitrexed-bound. Possible interaction routes between hydrophobic residues of the mTS protein N-terminal segment and the active site are also discussed.
| + | |
| - | | + | |
| - | Crystal structure of mouse thymidylate synthase in tertiary complex with dUMP and raltitrexed reveals N-terminus architecture and two different active site conformations.,Dowiercial A, Wilk P, Rypniewski W, Rode W, Jarmula A Biomed Res Int. 2014;2014:945803. doi: 10.1155/2014/945803. Epub 2014 Jun 3. PMID:24995339<ref>PMID:24995339</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4psg" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Thymidylate synthase|Thymidylate synthase]] | + | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymidylate synthase]]
| + | [[Category: Jarmula A]] |
| - | [[Category: Jarmula, A]] | + | [[Category: Rode W]] |
| - | [[Category: Rode, W]] | + | [[Category: Wilk P]] |
| - | [[Category: Wilk, P]] | + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Nucleotide biosynthesis]]
| + | |
| - | [[Category: Protein dimer]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
