4jef: Difference between revisions
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==Crystal structure of human thymidylate synthase Y202A in inactive conformation.== | ==Crystal structure of human thymidylate synthase Y202A in inactive conformation.== | ||
<StructureSection load='4jef' size='340' side='right' caption='[[4jef]], [[Resolution|resolution]] 2.31Å' scene=''> | <StructureSection load='4jef' size='340' side='right'caption='[[4jef]], [[Resolution|resolution]] 2.31Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jef]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JEF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JEF FirstGlance]. <br> | <table><tr><td colspan='2'>[[4jef]] is a 1 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=4JEF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JEF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e28|4e28]], [[3egy|3egy]], [[3ehi|3ehi]], [[4fgt|4fgt]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e28|4e28]], [[3egy|3egy]], [[3ehi|3ehi]], [[4fgt|4fgt]]</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='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='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=4jef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jef OCA], [http://pdbe.org/4jef PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jef RCSB], [http://www.ebi.ac.uk/pdbsum/4jef PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jef ProSAT]</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=4jef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jef OCA], [http://pdbe.org/4jef PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jef RCSB], [http://www.ebi.ac.uk/pdbsum/4jef PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jef ProSAT]</span></td></tr> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
[[Category: Stroud, R M]] | [[Category: Stroud, R M]] | ||
Revision as of 12:00, 3 April 2019
Crystal structure of human thymidylate synthase Y202A in inactive conformation.Crystal structure of human thymidylate synthase Y202A in inactive conformation.
Structural highlights
Function[TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1] Publication Abstract from PubMedHuman thymidylate synthase (hTS), a target for antiproliferative drugs, is an obligate homodimer. Single-point mutations to alanine at the monomer-monomer interface may enable the identification of specific residues that delineate sites for drugs aimed at perturbing the protein-protein interactions critical for activity. We computationally identified putative hotspot residues at the interface and designed mutants to perturb the intersubunit interaction. Dimer dissociation constants measured by a FRET-based assay range from 60 nM for wild-type hTS up to about 1 mM for single-point mutants and agree with computational predictions of the effects of these mutations. Mutations that are remote from the active site retain full or partial activity, although the substrate KM values were generally higher and the dimer was less stable. The lower dimer stability of the mutants can facilitate access to the dimer interface by small molecules and thereby aid the design of inhibitors that bind at the dimer interface. Hotspots in an obligate homodimeric anticancer target. Structural and functional effects of interfacial mutations in human thymidylate synthase.,Salo-Ahen OM, Tochowicz A, Pozzi C, Cardinale D, Ferrari S, Boum Y, Mangani S, Stroud RM, Saxena P, Myllykallio H, Costi MP, Ponterini G, Wade RC J Med Chem. 2015 Apr 23;58(8):3572-81. doi: 10.1021/acs.jmedchem.5b00137. Epub, 2015 Apr 1. PMID:25798950[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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