View source for 8b58


==Crystal Structure of Cyclophilin TgCyp23 from Toxoplasma gondii in complex with Cyclosporin A==
<StructureSection load='8b58' size='340' side='right'caption='[[8b58]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8b58]] 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=8B58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B58 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</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=8b58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b58 OCA], [https://pdbe.org/8b58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b58 RCSB], [https://www.ebi.ac.uk/pdbsum/8b58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b58 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]
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== Publication Abstract from PubMed ==
Cyclosporin (CsA) has antiparasite activity against the human pathogen Toxoplasma gondii. A possible mechanism of action involves CsA binding to T. gondii cyclophilins, although much remains to be understood. Herein, we characterize the functional and structural properties of a conserved (TgCyp23) and a more divergent (TgCyp18.4) cyclophilin isoform from T. gondii. While TgCyp23 is a highly active cis-trans-prolyl isomerase (PPIase) and binds CsA with nanomolar affinity, TgCyp18.4 shows low PPIase activity and is significantly less sensitive to CsA inhibition. The crystal structure of the TgCyp23:CsA complex was solved at the atomic resolution showing the molecular details of CsA recognition by the protein. Computational and structural studies revealed relevant differences at the CsA-binding site between TgCyp18.4 and TgCyp23, suggesting that the two cyclophilins might have distinct functions in the parasite. These studies highlight the extensive diversification of TgCyps and pave the way for antiparasite interventions based on selective targeting of cyclophilins.

Structural Basis for Cyclosporin Isoform-Specific Inhibition of Cyclophilins from Toxoplasma gondii.,Favretto F, Jimenez-Faraco E, Conter C, Dominici P, Hermoso JA, Astegno A ACS Infect Dis. 2023 Jan 18. doi: 10.1021/acsinfecdis.2c00566. PMID:36653744<ref>PMID:36653744</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Toxoplasma gondii]]
[[Category: Hermoso JA]]
[[Category: Jimenez-Faraco E]]