This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1f4g
From Proteopedia
(Difference between revisions)
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
==CRYSTAL STRUCTURE OF E. COLI THYMIDYLATE SYNTHASE COMPLEXED WITH SP-876== | ==CRYSTAL STRUCTURE OF E. COLI THYMIDYLATE SYNTHASE COMPLEXED WITH SP-876== | ||
| - | <StructureSection load='1f4g' size='340' side='right' caption='[[1f4g]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='1f4g' size='340' side='right'caption='[[1f4g]], [[Resolution|resolution]] 1.75Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1f4g]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1f4g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F4G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F4G FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MHO:S-OXYMETHIONINE'>MHO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TP4:N-[4-[[GLUTAMIC+ACID]-CARBONYL]-BENZENE-SULFONYL-D-PROLINYL]-3-AMINO-PROPANOIC+ACID'>TP4</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=1f4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4g OCA], [https://pdbe.org/1f4g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f4g RCSB], [https://www.ebi.ac.uk/pdbsum/1f4g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f4g ProSAT]</span></td></tr> | |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/TYSY_ECOLI TYSY_ECOLI] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation. |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 22: | Line 20: | ||
</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/main_output.php?pdb_ID=1f4g ConSurf]. | </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/main_output.php?pdb_ID=1f4g ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | We report a strategy (called "tethering") to discover low molecular weight ligands ( approximately 250 Da) that bind weakly to targeted sites on proteins through an intermediary disulfide tether. A native or engineered cysteine in a protein is allowed to react reversibly with a small library of disulfide-containing molecules ( approximately 1,200 compounds) at concentrations typically used in drug screening (10 to 200 microM). The cysteine-captured ligands, which are readily identified by MS, are among the most stable complexes, even though in the absence of the covalent tether the ligands may bind very weakly. This method was applied to generate a potent inhibitor for thymidylate synthase, an essential enzyme in pyrimidine metabolism with therapeutic applications in cancer and infectious diseases. The affinity of the untethered ligand (K(i) approximately 1 mM) was improved 3,000-fold by synthesis of a small set of analogs with the aid of crystallographic structures of the tethered complex. Such site-directed ligand discovery allows one to nucleate drug design from a spatially targeted lead fragment. | ||
| - | + | ==See Also== | |
| - | + | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | == | + | |
| - | + | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Escherichia coli]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Braisted | + | [[Category: Braisted AC]] |
| - | [[Category: Erlanson | + | [[Category: Erlanson DA]] |
| - | [[Category: Gordon | + | [[Category: Gordon E]] |
| - | [[Category: Randal | + | [[Category: Randal M]] |
| - | [[Category: Raphael | + | [[Category: Raphael DR]] |
| - | [[Category: Stroud | + | [[Category: Stroud RM]] |
| - | [[Category: Wells | + | [[Category: Wells JA]] |
| - | + | ||
| - | + | ||
Current revision
CRYSTAL STRUCTURE OF E. COLI THYMIDYLATE SYNTHASE COMPLEXED WITH SP-876
| |||||||||||
