6tz6: Difference between revisions

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-'''Unreleased structure'''
-The entry 6tz6 is ON HOLD  until Paper Publication
+==Crystal Structure of Candida Albicans Calcineurin A, Calcineurin B, FKBP12 and FK506 (Tacrolimus)==
+<StructureSection load='6tz6' size='340' side='right'caption='[[6tz6]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tz6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans_SC5314 Candida albicans SC5314] and [https://en.wikipedia.org/wiki/Candida_albicans_WO-1 Candida albicans WO-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TZ6 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]] 2.55&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FK5:8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN'>FK5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6tz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tz6 OCA], [https://pdbe.org/6tz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tz6 RCSB], [https://www.ebi.ac.uk/pdbsum/6tz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tz6 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/C4YFI3_CANAW C4YFI3_CANAW]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops. NMR analysis, molecular dynamic simulations, and mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved in hFKBP12, as critical for binding and inhibition of fungal calcineurin. These differences enable us to develop a less immunosuppressive FK506 analog, APX879, with an acetohydrazine substitution of the C22-carbonyl of FK506. APX879 exhibits reduced immunosuppressive activity and retains broad-spectrum antifungal activity and efficacy in a murine model of invasive fungal infection.
-Authors:
+Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.,Juvvadi PR, Fox D 3rd, Bobay BG, Hoy MJ, Gobeil SMC, Venters RA, Chang Z, Lin JJ, Averette AF, Cole DC, Barrington BC, Wheaton JD, Ciofani M, Trzoss M, Li X, Lee SC, Chen YL, Mutz M, Spicer LD, Schumacher MA, Heitman J, Steinbach WJ Nat Commun. 2019 Sep 19;10(1):4275. doi: 10.1038/s41467-019-12199-1. PMID:31537789<ref>PMID:31537789</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6tz6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calcineurin 3D structures|Calcineurin 3D structures]]
+*[[FKBP 3D structures|FKBP 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Candida albicans SC5314]]
+[[Category: Candida albicans WO-1]]
+[[Category: Large Structures]]
+[[Category: Fox III D]]
+[[Category: Lukacs CM]]