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6t98: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6t98]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_infantum Leishmania infantum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T98 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6t98]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_infantum Leishmania infantum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T98 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MWZ:4-[3-methyl-1-[4-[4-(2-phenylethyl)-1,3-thiazol-2-yl]-3-(2-piperidin-4-ylethoxy)phenyl]-1,2,3-triazol-3-ium-4-yl]butan-1-amine'>MWZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MWZ:4-[3-methyl-1-[4-[4-(2-phenylethyl)-1,3-thiazol-2-yl]-3-(2-piperidin-4-ylethoxy)phenyl]-1,2,3-triazol-3-ium-4-yl]butan-1-amine'>MWZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6t98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t98 OCA], [https://pdbe.org/6t98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t98 RCSB], [https://www.ebi.ac.uk/pdbsum/6t98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t98 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=6t98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t98 OCA], [https://pdbe.org/6t98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t98 RCSB], [https://www.ebi.ac.uk/pdbsum/6t98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t98 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/A4HSF7_LEIIN A4HSF7_LEIIN]  
[https://www.uniprot.org/uniprot/A4HSF7_LEIIN A4HSF7_LEIIN]  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N-methylation of the triazole moiety present in our recently described triazole-phenyl-thiazole dimerization disruptors of Leishmania infantum trypanothione disulfide reductase (LiTryR) led to a new class of potent inhibitors that target different binding sites on this enzyme. Subtle structural changes among representative library members modified their mechanism of action, switching from models of classical competitive inhibition to time-dependent mixed noncompetitive inhibition. X-ray crystallography and molecular modeling results provided a rationale for this distinct behavior. The remarkable potency and selectivity improvements, particularly against intracellular amastigotes, of the LiTryR dimerization disruptors 4c and 4d reveal that they could be exploited as leishmanicidal agents. Of note, L. infantum promastigotes treated with 4c significantly reduced their low-molecular-weight thiol content, thus providing additional evidence that LiTryR is the main target of this novel compound.
Identification of 1,2,3-triazolium salt-based inhibitors of Leishmania infantum trypanothione disulfide reductase with enhanced antileishmanial potency in cellulo and increased selectivity.,de Lucio H, Revuelto A, Carriles AA, de Castro S, Garcia-Gonzalez S, Garcia-Soriano JC, Alcon-Calderon M, Sanchez-Murcia PA, Hermoso JA, Gago F, Camarasa MJ, Jimenez-Ruiz A, Velazquez S Eur J Med Chem. 2022 Dec 15;244:114878. doi: 10.1016/j.ejmech.2022.114878. Epub , 2022 Oct 29. PMID:36332553<ref>PMID:36332553</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6t98" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Trypanothione reductase|Trypanothione reductase]]
*[[Trypanothione reductase|Trypanothione reductase]]
== References ==
<references/>
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</StructureSection>
</StructureSection>

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