3c06: Difference between revisions

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-{{Seed}}
-[[Image:3c06.jpg|left|200px]]
-<!--
+==Lactobacillus CASEI Thymidylate Synthase Ternary Complex With DUMP and the Phtalimidic Derivative 14C in Multiple Binding Modes-Mode 1==
-The line below this paragraph, containing "STRUCTURE_3c06", creates the "Structure Box" on the page.
+<StructureSection load='3c06' size='340' side='right'caption='[[3c06]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3c06]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lacticaseibacillus_casei Lacticaseibacillus casei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C06 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=14C:2-(2-CHLOROPYRIDIN-4-YL)-4-METHYL-1H-ISOINDOLE-1,3(2H)-DIONE'>14C</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-{{STRUCTURE_3c06|  PDB=3c06  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c06 OCA], [https://pdbe.org/3c06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c06 RCSB], [https://www.ebi.ac.uk/pdbsum/3c06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c06 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA] Provides the sole de novo source of dTMP for DNA biosynthesis.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/3c06_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=3c06 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+To identify specific bacterial thymidylate synthase (TS) inhibitors, we exploited phenolphthalein (PTH), which inhibits both bacterial and human enzymes. The X-ray crystal structure of Lactobacillus casei TS (LcTS) that binds PTH showed multiple binding modes of the inhibitor, which prevented a classical structure-based drug design approach. To overcome this issue, we synthesized two phthalimidic libraries that were tested against TS enzymes and then we performed X-ray crystallographic screening of the active compounds. Compounds 6A, 8A, and 12A showed 40-fold higher affinity for bacterial TS than human TS. The X-ray crystallographic screening characterized the binding mode of six inhibitors in complexes with LcTS. Of these, 20A, 23A, and 24A showed a common unique binding mode, whereas 8A showed a different, unique binding mode. A comparative analysis of the LcTS X-ray complexes that were obtained with the pathogenic TS enabled the selection of compounds 8A and 23A as specific compounds and starting points to be exploited for the specific inhibition of pathogen enzymes.
-===Lactobacillus CASEI Thymidylate Synthase Ternary Complex With DUMP and the Phtalimidic Derivative 14C in Multiple Binding Modes-Mode 1===
+Identification of the binding modes of N-phenylphthalimides inhibiting bacterial thymidylate synthase through X-ray crystallography screening.,Mangani S, Cancian L, Leone R, Pozzi C, Lazzari S, Luciani R, Ferrari S, Costi MP J Med Chem. 2011 Aug 11;54(15):5454-67. Epub 2011 Jul 12. PMID:21696158<ref>PMID:21696158</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3c06" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-C06 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C06 OCA].
+*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
-[[Category: Lactobacillus casei]]
+== References ==
-[[Category: Thymidylate synthase]]
+<references/>
-[[Category: Cancian, L.]]
+__TOC__
-[[Category: Costi, M P.]]
+</StructureSection>
-[[Category: Ferrari, S.]]
+[[Category: Lacticaseibacillus casei]]
-[[Category: Leone, R.]]
+[[Category: Large Structures]]
-[[Category: Luciani, R.]]
+[[Category: Cancian L]]
-[[Category: Mangani, S.]]
+[[Category: Costi MP]]
-[[Category: Cytoplasm]]
+[[Category: Ferrari S]]
-[[Category: Methyltransferase]]
+[[Category: Leone R]]
-[[Category: Nucleotide biosynthesis]]
+[[Category: Luciani R]]
-[[Category: Structure-based drug design]]
+[[Category: Mangani S]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 21 10:43:24 2009''