7t0e - Revision history

OCA at 16:56, 18 October 2023

OCA — Wed, 18 Oct 2023 16:56:42 GMT

←Older revision		Revision as of 16:56, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7t0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T0E FirstGlance]. <br>		<table><tr><td colspan='2'>[[7t0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T0E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=XOA:(5S)-4-({1-[(4-bromophenyl)methyl]-1H-imidazol-5-yl}methyl)-5-butyl-1-(3-chlorophenyl)piperazin-2-one'>XOA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 2.223Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=XOA:(5S)-4-({1-[(4-bromophenyl)methyl]-1H-imidazol-5-yl}methyl)-5-butyl-1-(3-chlorophenyl)piperazin-2-one'>XOA</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=7t0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t0e OCA], [https://pdbe.org/7t0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t0e RCSB], [https://www.ebi.ac.uk/pdbsum/7t0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t0e ProSAT]</span></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=7t0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t0e OCA], [https://pdbe.org/7t0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t0e RCSB], [https://www.ebi.ac.uk/pdbsum/7t0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t0e ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7t0e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7t0e" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Farnesyltransferase 3D structures\|Farnesyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:22, 9 November 2022

OCA — Wed, 09 Nov 2022 07:22:31 GMT

←Older revision		Revision as of 07:22, 9 November 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7t0e is ~~ON HOLD until Paper~~ Publication	+	==Cryptococcus neoformans protein farnesyltransferase in complex with FPP and inhibitor 2b==
		+	<StructureSection load='7t0e' size='340' side='right'caption='[[7t0e]], [[Resolution\|resolution]] 2.22Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7t0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T0E FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=XOA:(5S)-4-({1-[(4-bromophenyl)methyl]-1H-imidazol-5-yl}methyl)-5-butyl-1-(3-chlorophenyl)piperazin-2-one'>XOA</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=7t0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t0e OCA], [https://pdbe.org/7t0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t0e RCSB], [https://www.ebi.ac.uk/pdbsum/7t0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t0e ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/J9VSJ6_CRYNH J9VSJ6_CRYNH]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Infections by fungal pathogens are difficult to treat due to a paucity of antifungals and emerging resistances. Next-generation antifungals therefore are needed urgently. We have developed compounds that prevent farnesylation of Cryptoccoccus neoformans Ras protein by inhibiting protein farnesyltransferase with 3-4 nanomolar affinities. Farnesylation directs Ras to the cell membrane and is required for infectivity of this lethal pathogenic fungus. Our high-affinity compounds inhibit fungal growth with 3-6 micromolar minimum inhibitory concentrations (MICs), 4- to 8-fold better than Fluconazole, an antifungal commonly used in the clinic. Compounds bound with distinct inhibition mechanisms at two alternative, partially overlapping binding sites, accessed via different inhibitor conformations. We showed that antifungal potency depends critically on the selected inhibition mechanism because this determines the efficacy of an inhibitor at low in vivo levels of enzyme and farnesyl substrate. We elucidated how chemical modifications of the antifungals encode desired inhibitor conformation and concomitant inhibitory mechanism.

-	~~Authors~~:	+	Structure-Guided Discovery of Potent Antifungals that Prevent Ras Signaling by Inhibiting Protein Farnesyltransferase.,Wang Y, Xu F, Nichols CB, Shi Y, Hellinga HW, Alspaugh JA, Distefano MD, Beese LS J Med Chem. 2022 Oct 11. doi: 10.1021/acs.jmedchem.2c00902. PMID:36218371<ref>PMID:36218371</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7t0e" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cryptococcus neoformans var. grubii H99]]
		+	[[Category: Large Structures]]
		+	[[Category: Beese LS]]
		+	[[Category: Shi Y]]
		+	[[Category: Wang Y]]

OCA at 09:18, 5 January 2022

OCA — Wed, 05 Jan 2022 09:18:53 GMT

←Older revision		Revision as of 09:18, 5 January 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7t0e is ON HOLD	+	The entry 7t0e is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7t0e" [edit=sysop:move=sysop]

OCA — Wed, 08 Dec 2021 08:37:01 GMT

Protected "7t0e" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:37, 8 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t0e is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Dec 2021 08:36:59 GMT

New page: '''Unreleased structure''' The entry 7t0e is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7t0e is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]