3sfy - Revision history

OCA at 09:50, 1 March 2024

OCA — Fri, 01 Mar 2024 09:50:21 GMT

←Older revision		Revision as of 09:50, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='3sfy' size='340' side='right'caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='3sfy' size='340' side='right'caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Crynh Crynh~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SFY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sfy]] 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=3SFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SFY 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=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.1Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</div></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=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [https://pdbe.org/3sfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [https://www.ebi.ac.uk/pdbsum/3sfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfy 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=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [https://pdbe.org/3sfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [https://www.ebi.ac.uk/pdbsum/3sfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfy ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/Q55S71_CRYNB Q55S71_CRYNB]
-	Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities and differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.	+
-		+
-	Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens.,Hast MA, Nichols CB, Armstrong SM, Kelly SM, Hellinga HW, Alspaugh JA, Beese LS J Biol Chem. 2011 Oct 7;286(40):~~35149-62. Epub 2011 Aug 4. PMID:21816822<ref>PMID:21816822<~~/~~ref>~~	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 3sfy" style="background-color:#fffaf0;"><~~/~~div>~~	+

	==See Also==		==See Also==
	*[[Farnesyltransferase 3D structures\|Farnesyltransferase 3D structures]]		*[[Farnesyltransferase 3D structures\|Farnesyltransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Crynh~~]]	+	[[Category: Cryptococcus neoformans var. grubii H99]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Beese~~, L S~~]]	+	[[Category: Beese LS]]
-	[[Category: Hast~~, M A]]~~	+	[[Category: Hast MA]]
-	~~[[Category: Prenyltransferase]]~~	+
-	~~[[Category: Protein farnesyltransferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:54, 29 June 2022

OCA — Wed, 29 Jun 2022 07:54:40 GMT

←Older revision		Revision as of 07:54, 29 June 2022
Line 1:		Line 1:

	==Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2==		==Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2==
-	<StructureSection load='3sfy' size='340' side='right' caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='3sfy' size='340' side='right'caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Crynh Crynh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SFY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Crynh Crynh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SFY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</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=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [~~http~~://pdbe.org/3sfy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3sfy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfy 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=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [https://pdbe.org/3sfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [https://www.ebi.ac.uk/pdbsum/3sfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfy ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 19:		Line 19:

	==See Also==		==See Also==
-	*[[Farnesyltransferase\|Farnesyltransferase]]	+	*[[Farnesyltransferase 3D structures\|Farnesyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Crynh]]		[[Category: Crynh]]
		+	[[Category: Large Structures]]
	[[Category: Beese, L S]]		[[Category: Beese, L S]]
	[[Category: Hast, M A]]		[[Category: Hast, M A]]

OCA at 11:25, 10 December 2016

OCA — Sat, 10 Dec 2016 11:25:21 GMT

←Older revision		Revision as of 11:25, 10 December 2016
Line 1:		Line 1:
		+
	==Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2==		==Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2==
	<StructureSection load='3sfy' size='340' side='right' caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='3sfy' size='340' side='right' caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Cryptococcus_neoformans Cryptococcus neoformans~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SFY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Crynh Crynh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SFY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [http://www.ebi.ac.uk/pdbsum/3sfy PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [http://pdbe.org/3sfy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [http://www.ebi.ac.uk/pdbsum/3sfy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfy ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 15:		Line 16:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3sfy" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 22:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cryptococcus neoformans~~]]	+	[[Category: Crynh]]
	[[Category: Beese, L S]]		[[Category: Beese, L S]]
	[[Category: Hast, M A]]		[[Category: Hast, M A]]

OCA at 11:10, 9 December 2014

OCA — Tue, 09 Dec 2014 11:10:11 GMT

←Older revision		Revision as of 11:10, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3sfy.~~png~~\|~~left~~\|~~200px~~]]	+	==Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2==
		+	<StructureSection load='3sfy' size='340' side='right' caption='[[3sfy]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SFY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FX:(2R)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3FX</scene>, <scene name='pdbligand=3FY:N-(2-{(4-BROMOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-N-(2-METHYLBENZYL)-1H-IMIDAZOLE-4-SULFONAMIDE'>3FY</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q73\|3q73]], [[3q75\|3q75]], [[3q78\|3q78]], [[3q79\|3q79]], [[3q7a\|3q7a]], [[3q7f\|3q7f]], [[3sfx\|3sfx]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sfy RCSB], [http://www.ebi.ac.uk/pdbsum/3sfy PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities and differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.

-	~~{{STRUCTURE_3sfy\| PDB=3sfy \| SCENE= }}~~	+	Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens.,Hast MA, Nichols CB, Armstrong SM, Kelly SM, Hellinga HW, Alspaugh JA, Beese LS J Biol Chem. 2011 Oct 7;286(40):35149-62. Epub 2011 Aug 4. PMID:21816822<ref>PMID:21816822</ref>

-	~~===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21816822}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3sfy]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].~~	+

	==See Also==		==See Also==
	*[[Farnesyltransferase\|Farnesyltransferase]]		*[[Farnesyltransferase\|Farnesyltransferase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021816822<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Cryptococcus neoformans]]		[[Category: Cryptococcus neoformans]]
-	[[Category: Beese, L S.]]	+	[[Category: Beese, L S]]
-	[[Category: Hast, M A.]]	+	[[Category: Hast, M A]]
	[[Category: Prenyltransferase]]		[[Category: Prenyltransferase]]
	[[Category: Protein farnesyltransferase]]		[[Category: Protein farnesyltransferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:12, 20 October 2012

OCA — Sat, 20 Oct 2012 10:12:03 GMT

←Older revision		Revision as of 10:12, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3sfy]] is a 2 chain structure ~~of [[Farnesyltransferase]]~~ with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].	+	[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].

	==See Also==		==See Also==

OCA at 01:19, 26 July 2012

OCA — Thu, 26 Jul 2012 01:19:08 GMT

←Older revision		Revision as of 01:19, 26 July 2012
Line 1:		Line 1:
	[[Image:3sfy.png\|left\|200px]]		[[Image:3sfy.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3sfy", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3sfy\| PDB=3sfy \| SCENE= }}		{{STRUCTURE_3sfy\| PDB=3sfy \| SCENE= }}

	===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===		===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21816822}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21816822 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21816822}}		{{ABSTRACT_PUBMED_21816822}}

	==About this Structure==		==About this Structure==
-	[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].	+	[[3sfy]] is a 2 chain structure of [[Farnesyltransferase]] with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].
		+
		+	==See Also==
		+	*[[Farnesyltransferase\|Farnesyltransferase]]

	==Reference==		==Reference==

OCA at 07:52, 30 October 2011

OCA — Sun, 30 Oct 2011 07:52:08 GMT

←Older revision		Revision as of 07:52, 30 October 2011
Line 1:		Line 1:
-	[[Image:3sfy.~~jpg~~\|left\|200px]]	+	[[Image:3sfy.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===		===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21816822}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21816822 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21816822}}

	==About this Structure==		==About this Structure==
	[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].		[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021816822</ref><references group="xtra"/>
	[[Category: Cryptococcus neoformans]]		[[Category: Cryptococcus neoformans]]
	[[Category: Beese, L S.]]		[[Category: Beese, L S.]]

OCA at 09:02, 3 August 2011

OCA — Wed, 03 Aug 2011 09:02:45 GMT

←Older revision		Revision as of 09:02, 3 August 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3sfy.jpg\|left\|200px]]

-	The ~~entry 3sfy~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3sfy", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3sfy\| PDB=3sfy \| SCENE= }}

-	~~Authors: Hast, M.A., Beese, L.S.~~	+	===Cryptococcus neoformans protein farnesyltransferase in complex with FPT-II and ethylenediamine inhibitor 2===

-	~~Description~~: ~~FTase~~ complex 8	+
		+	==About this Structure==
		+	[[3sfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFY OCA].
		+	[[Category: Cryptococcus neoformans]]
		+	[[Category: Beese, L S.]]
		+	[[Category: Hast, M A.]]
		+	[[Category: Prenyltransferase]]
		+	[[Category: Protein farnesyltransferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "3sfy" [edit=sysop:move=sysop]

OCA — Wed, 22 Jun 2011 16:23:19 GMT

Protected "3sfy" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:23, 22 June 2011

OCA: New page: '''Unreleased structure''' The entry 3sfy is ON HOLD Authors: Hast, M.A., Beese, L.S. Description: FTase complex 8

OCA — Wed, 22 Jun 2011 16:23:18 GMT

New page: '''Unreleased structure''' The entry 3sfy is ON HOLD Authors: Hast, M.A., Beese, L.S. Description: FTase complex 8

New page

'''Unreleased structure'''

The entry 3sfy is ON HOLD

Authors: Hast, M.A., Beese, L.S.

Description: FTase complex 8