8r7t
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Cyclophilin TgCyp23 from Toxoplasma gondii in complex with Alisporivir (nonimmunosuppressive analogue of Cyclosporin)== | |
| + | <StructureSection load='8r7t' size='340' side='right'caption='[[8r7t]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8r7t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R7T FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=33X:N-METHYL-D-ALANINE'>33X</scene>, <scene name='pdbligand=66E:N-ethyl-L-valine'>66E</scene>, <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</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=8r7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r7t OCA], [https://pdbe.org/8r7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r7t RCSB], [https://www.ebi.ac.uk/pdbsum/8r7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r7t ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A7J6KAD1_TOXGO A0A7J6KAD1_TOXGO] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.[RuleBase:RU363019] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets. However, CsA immunosuppressive nature hinders its use as an antitoxoplasmosis agent. Here, we evaluate the potential of three CsA derivatives devoid of immunosuppressive activity, namely, NIM811, Alisporivir, and dihydrocyclosporin A to target a previously characterized cyclophilin from Toxoplasma gondii (TgCyp23). We determined the X-ray crystal structures of TgCyp23 in complex with the three analogs and elucidated their binding and inhibitory properties. The high resolution of the structures revealed the precise positioning of ligands within the TgCyp23 binding site and the details of protein-ligand interactions. A comparison with the established ternary structure involving calcineurin indicates that substitutions at position 4 in CsA derivatives prevent calcineurin binding. This finding provides a molecular explanation for why CsA analogs can target Toxoplasma cyclophilins without compromising the human immune response. | ||
| - | + | Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.,Favretto F, Jimenez-Faraco E, Catucci G, Di Matteo A, Travaglini-Allocatelli C, Sadeghi SJ, Dominici P, Hermoso JA, Astegno A Protein Sci. 2024 Oct;33(10):e5157. doi: 10.1002/pro.5157. PMID:39312281<ref>PMID:39312281</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8r7t" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Toxoplasma gondii]] | ||
| + | [[Category: Hermoso JA]] | ||
| + | [[Category: Jimenez-Faraco E]] | ||
Current revision
Crystal Structure of Cyclophilin TgCyp23 from Toxoplasma gondii in complex with Alisporivir (nonimmunosuppressive analogue of Cyclosporin)
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