7k9r - Revision history

OCA at 15:20, 18 October 2023

OCA — Wed, 18 Oct 2023 15:20:05 GMT

←Older revision		Revision as of 15:20, 18 October 2023
Line 1:		Line 1:

	==Cryptococcus neoformans Hsp90 nucleotide binding domain==		==Cryptococcus neoformans Hsp90 nucleotide binding domain==
-	<StructureSection load='7k9r' size='340' side='right'caption='[[7k9r]]' scene=''>	+	<StructureSection load='7k9r' size='340' side='right'caption='[[7k9r]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K9R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7k9r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K9R FirstGlance]. <br>
-	</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=7k9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k9r OCA], [https://pdbe.org/7k9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k9r RCSB], [https://www.ebi.ac.uk/pdbsum/7k9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k9r ProSAT]</span></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]] 1.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7k9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k9r OCA], [https://pdbe.org/7k9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k9r RCSB], [https://www.ebi.ac.uk/pdbsum/7k9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k9r ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/J9VVA4_CRYNH J9VVA4_CRYNH]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many of which govern thermotolerance, virulence, and drug resistance in fungal species. However, use of Hsp90 inhibitors as antifungal therapeutics has been precluded by human host toxicities and suppression of immune responses. We recently described resorcylate aminopyrazoles (RAPs) as the first class of Hsp90 inhibitors capable of discriminating between fungal (Cryptococcus neoformans, Candida albicans) and human isoforms of Hsp90 in biochemical assays. Here, we report an iterative structure-property optimization toward RAPs capable of inhibiting C. neoformans growth in culture. In addition, we report the first X-ray crystal structures of C. neoformans Hsp90 nucleotide binding domain (NBD), as the apoprotein and in complexes with the non-species-selective Hsp90 inhibitor NVP-AUY922 and three RAPs revealing unique ligand-induced conformational rearrangements, which reaffirm the hypothesis that intrinsic differences in protein flexibility can confer selective inhibition of fungal versus human Hsp90 isoforms.
		+
		+	Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors: Optimization of Whole-Cell Anticryptococcal Activity and Insights into the Structural Origins of Cryptococcal Selectivity.,Marcyk PT, LeBlanc EV, Kuntz DA, Xue A, Ortiz F, Trilles R, Bengtson S, Kenney TMG, Huang DS, Robbins N, Williams NS, Krysan DJ, Prive GG, Whitesell L, Cowen LE, Brown LE J Med Chem. 2021 Jan 14. doi: 10.1021/acs.jmedchem.0c01777. PMID:33444025<ref>PMID:33444025</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7k9r" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Cryptococcus neoformans]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kenney T]]		[[Category: Kenney T]]
	[[Category: Kuntz DA]]		[[Category: Kuntz DA]]
	[[Category: Prive GG]]		[[Category: Prive GG]]

OCA at 07:58, 27 January 2021

OCA — Wed, 27 Jan 2021 07:58:13 GMT

←Older revision		Revision as of 07:58, 27 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7k9r ~~is ON HOLD until Paper Publication~~	+	==Cryptococcus neoformans Hsp90 nucleotide binding domain==
-		+	<StructureSection load='7k9r' size='340' side='right'caption='[[7k9r]]' scene=''>
-	~~Authors~~: ~~Kuntz~~, D.A., ~~Kenney~~, T., ~~Prive~~, G.G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K9R FirstGlance]. <br>
-	~~Description: Cryptococcus neoformans Hsp90 nucleotide binding domain~~	+	</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=7k9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k9r OCA], [https://pdbe.org/7k9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k9r RCSB], [https://www.ebi.ac.uk/pdbsum/7k9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k9r ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Prive, G.G~~]]	+	__TOC__
-	[[Category: ~~Kenney, T~~]]	+	</StructureSection>
-	[[Category: ~~Kuntz, D.A~~]]	+	[[Category: Large Structures]]
		+	[[Category: Kenney T]]
		+	[[Category: Kuntz DA]]
		+	[[Category: Prive GG]]

OCA: Protected "7k9r" [edit=sysop:move=sysop]

OCA — Wed, 07 Oct 2020 04:49:27 GMT

Protected "7k9r" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:49, 7 October 2020

OCA: New page: '''Unreleased structure''' The entry 7k9r is ON HOLD until Paper Publication Authors: Kuntz, D.A., Kenney, T., Prive, G.G. Description: Cryptococcus neoformans Hsp90 nucleotide binding...

OCA — Wed, 07 Oct 2020 04:49:26 GMT

New page: '''Unreleased structure''' The entry 7k9r is ON HOLD until Paper Publication Authors: Kuntz, D.A., Kenney, T., Prive, G.G. Description: Cryptococcus neoformans Hsp90 nucleotide binding...

New page

'''Unreleased structure'''

The entry 7k9r is ON HOLD until Paper Publication

Authors: Kuntz, D.A., Kenney, T., Prive, G.G.

Description: Cryptococcus neoformans Hsp90 nucleotide binding domain
[[Category: Unreleased Structures]]
[[Category: Prive, G.G]]
[[Category: Kenney, T]]
[[Category: Kuntz, D.A]]