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<StructureSection load='1f4c' size='340' side='right'caption='[[1f4c]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='1f4c' size='340' side='right'caption='[[1f4c]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1f4c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F4C FirstGlance]. <br>
<table><tr><td colspan='2'>[[1f4c]] 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=1F4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F4C FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TP2:N-[TOSYL-D-PROLINYL]AMINO-ETHANETHIOL'>TP2</scene></td></tr>
</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&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene></td></tr>
<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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TP2:N-[TOSYL-D-PROLINYL]AMINO-ETHANETHIOL'>TP2</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1f4b|1f4b]], [[1f4d|1f4d]], [[1f4e|1f4e]], [[1f4f|1f4f]], [[1f4g|1f4g]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1f4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4c OCA], [https://pdbe.org/1f4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f4c RCSB], [https://www.ebi.ac.uk/pdbsum/1f4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f4c ProSAT]</span></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=1f4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4c OCA], [https://pdbe.org/1f4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f4c RCSB], [https://www.ebi.ac.uk/pdbsum/1f4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f4c ProSAT]</span></td></tr>
</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.  
[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]]
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</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=1f4c 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=1f4c 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.
Site-directed ligand discovery.,Erlanson DA, Braisted AC, Raphael DR, Randal M, Stroud RM, Gordon EM, Wells JA Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9367-72. PMID:10944209<ref>PMID:10944209</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1f4c" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Thymidylate synthase]]
[[Category: Braisted AC]]
[[Category: Braisted, A C]]
[[Category: Erlanson DA]]
[[Category: Erlanson, D A]]
[[Category: Gordon E]]
[[Category: Gordon, E]]
[[Category: Randal M]]
[[Category: Randal, M]]
[[Category: Raphael DR]]
[[Category: Raphael, D R]]
[[Category: Stroud RM]]
[[Category: Stroud, R M]]
[[Category: Wells JA]]
[[Category: Wells, J A]]
[[Category: E. coli thymidylate synthase modified at cysteine 146]]
[[Category: Transferase]]

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