6tz7: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6tz7 is ON HOLD  until Paper Publication
+==Crystal Structure of Aspergillus fumigatus Calcineurin A, Calcineurin B, FKBP12 and FK506 (Tacrolimus)==
+<StructureSection load='6tz7' size='340' side='right'caption='[[6tz7]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tz7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TZ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TZ7 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]] 2.5&#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=6tz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tz7 OCA], [https://pdbe.org/6tz7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tz7 RCSB], [https://www.ebi.ac.uk/pdbsum/6tz7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tz7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PP2B_ASPFU PP2B_ASPFU] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
+<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 6tz7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calcineurin 3D structures|Calcineurin 3D structures]]
+*[[FKBP 3D structures|FKBP 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Aspergillus fumigatus Af293]]
+[[Category: Large Structures]]
+[[Category: Fox III D]]
+[[Category: Horanyi PS]]