4up1: Difference between revisions
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==Crystal structure of native human Thymidylate synthase in active form== | |||
<StructureSection load='4up1' size='340' side='right'caption='[[4up1]], [[Resolution|resolution]] 2.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4up1]] is a 4 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=4UP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UP1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.991Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4up1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4up1 OCA], [https://pdbe.org/4up1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4up1 RCSB], [https://www.ebi.ac.uk/pdbsum/4up1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4up1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== Publication Abstract from PubMed == | |||
Human thymidylate synthase (hTS) provides the sole de novo intracellular source of thymidine 5'-monophosphate (dTMP). hTS is required for DNA replication prior to cell division, making it an attractive target for anticancer chemotherapy and drug discovery. hTS binds 2'-deoxyuridine 5'-monophosphate (dUMP) and the folate co-substrate N5,N10-methylenetetrahydrofolate (meTHF) in a pocket near the catalytic residue Cys195. The catalytic loop, which is composed of amino-acid residues 181-197, can adopt two distinct conformations related by a 180 degrees rotation. In the active conformation Cys195 is close to the active site, while in the inactive conformation it is rotated and Cys195 is too distant from the active site for catalysis. Several hTS structures, either native or engineered, have been solved in the active conformation in complex with ligands or inhibitors and at different salt concentrations. However, apo hTS structures have been solved in an inactive conformation in high-salt and low-salt conditions (PDB entries 1ypv, 4h1i, 4gyh, 3egy and 3ehi). Here, the structure of apo hTS crystallized in the active form with sulfate ions coordinated by the arginine residue that binds dUMP is reported. | |||
Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.,Deschamps P, Rety S, Bareille J, Leulliot N Acta Crystallogr F Struct Biol Commun. 2017 Jun 1;73(Pt 6):336-341. doi:, 10.1107/S2053230X17007233. Epub 2017 May 25. PMID:28580921<ref>PMID:28580921</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4up1" style="background-color:#fffaf0;"></div> | ||
[[Category: Deschamps | |||
[[Category: Leulliot | ==See Also== | ||
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Deschamps P]] | |||
[[Category: Leulliot N]] | |||
[[Category: Rety S]] | |||
Latest revision as of 13:32, 10 January 2024
Crystal structure of native human Thymidylate synthase in active formCrystal structure of native human Thymidylate synthase in active form
Structural highlights
FunctionTYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1] Publication Abstract from PubMedHuman thymidylate synthase (hTS) provides the sole de novo intracellular source of thymidine 5'-monophosphate (dTMP). hTS is required for DNA replication prior to cell division, making it an attractive target for anticancer chemotherapy and drug discovery. hTS binds 2'-deoxyuridine 5'-monophosphate (dUMP) and the folate co-substrate N5,N10-methylenetetrahydrofolate (meTHF) in a pocket near the catalytic residue Cys195. The catalytic loop, which is composed of amino-acid residues 181-197, can adopt two distinct conformations related by a 180 degrees rotation. In the active conformation Cys195 is close to the active site, while in the inactive conformation it is rotated and Cys195 is too distant from the active site for catalysis. Several hTS structures, either native or engineered, have been solved in the active conformation in complex with ligands or inhibitors and at different salt concentrations. However, apo hTS structures have been solved in an inactive conformation in high-salt and low-salt conditions (PDB entries 1ypv, 4h1i, 4gyh, 3egy and 3ehi). Here, the structure of apo hTS crystallized in the active form with sulfate ions coordinated by the arginine residue that binds dUMP is reported. Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.,Deschamps P, Rety S, Bareille J, Leulliot N Acta Crystallogr F Struct Biol Commun. 2017 Jun 1;73(Pt 6):336-341. doi:, 10.1107/S2053230X17007233. Epub 2017 May 25. PMID:28580921[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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