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3q7f

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==Cryptococcus neoformans protein farnesyltransferase in complex with FPP and ethylenediamine inhibitor 1==
==Cryptococcus neoformans protein farnesyltransferase in complex with FPP and ethylenediamine inhibitor 1==
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<StructureSection load='3q7f' size='340' side='right' caption='[[3q7f]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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<StructureSection load='3q7f' size='340' side='right'caption='[[3q7f]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3q7f]] 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=3Q7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q7F FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3q7f]] 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=3Q7F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q7F FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3CX:(2S)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3CX</scene>, <scene name='pdbligand=ED2:N-BENZYL-N-(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>ED2</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<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]], [[3sfx|3sfx]], [[3sfy|3sfy]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3CX:(2S)-3-(CYCLOHEXYLAMINO)-2-HYDROXYPROPANE-1-SULFONIC+ACID'>3CX</scene>, <scene name='pdbligand=ED2:N-BENZYL-N-(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>ED2</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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=3q7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q7f OCA], [http://pdbe.org/3q7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q7f RCSB], [http://www.ebi.ac.uk/pdbsum/3q7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q7f ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3q7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q7f OCA], [https://pdbe.org/3q7f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q7f RCSB], [https://www.ebi.ac.uk/pdbsum/3q7f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q7f ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q55S71_CRYNB Q55S71_CRYNB]
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3q7f" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Farnesyltransferase|Farnesyltransferase]]
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*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Crynh]]
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[[Category: Cryptococcus neoformans var. grubii H99]]
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[[Category: Beese, L S]]
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[[Category: Large Structures]]
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[[Category: Hast, M A]]
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[[Category: Beese LS]]
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[[Category: Protein prenyltransferase]]
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[[Category: Hast MA]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Cryptococcus neoformans protein farnesyltransferase in complex with FPP and ethylenediamine inhibitor 1

PDB ID 3q7f

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