3ik1: Difference between revisions
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==Lactobacillus casei Thymidylate Synthase in Ternary Complex with dUMP and the Phtalimidic Derivative 20C== | ==Lactobacillus casei Thymidylate Synthase in Ternary Complex with dUMP and the Phtalimidic Derivative 20C== | ||
<StructureSection load='3ik1' size='340' side='right' caption='[[3ik1]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='3ik1' size='340' side='right'caption='[[3ik1]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ik1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IK1 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[3ik1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IK1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3IK1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20C:2-HYDROXY-4-(4-METHYL-1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)BENZOIC+ACID'>20C</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=20C:2-HYDROXY-4-(4-METHYL-1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)BENZOIC+ACID'>20C</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bnz|3bnz]], [[3byx|3byx]], [[3c06|3c06]], [[3c0a|3c0a]], [[3bz0|3bz0]], [[3ijz|3ijz]], [[3ik0|3ik0]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bnz|3bnz]], [[3byx|3byx]], [[3c06|3c06]], [[3c0a|3c0a]], [[3bz0|3bz0]], [[3ijz|3ijz]], [[3ik0|3ik0]]</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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3ik1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ik1 OCA], [http://pdbe.org/3ik1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ik1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ik1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ik1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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==See Also== | ==See Also== | ||
*[[Thymidylate synthase|Thymidylate synthase]] | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Bacillus a von freudenreich 1890]] | [[Category: Bacillus a von freudenreich 1890]] | ||
[[Category: Large Structures]] | |||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
[[Category: Cancian, L]] | [[Category: Cancian, L]] | ||
Revision as of 14:57, 23 September 2020
Lactobacillus casei Thymidylate Synthase in Ternary Complex with dUMP and the Phtalimidic Derivative 20CLactobacillus casei Thymidylate Synthase in Ternary Complex with dUMP and the Phtalimidic Derivative 20C
Structural highlights
Function[TYSY_LACCA] Provides the sole de novo source of dTMP for DNA biosynthesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTo 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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