3o6o

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==Crystal Structure of the N-terminal domain of an HSP90 from Trypanosoma Brucei, Tb10.26.1080 in the presence of an the inhibitor BIIB021==
==Crystal Structure of the N-terminal domain of an HSP90 from Trypanosoma Brucei, Tb10.26.1080 in the presence of an the inhibitor BIIB021==
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<StructureSection load='3o6o' size='340' side='right' caption='[[3o6o]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='3o6o' size='340' side='right'caption='[[3o6o]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3o6o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O6O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3o6o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O6O 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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=94M:6-CHLORO-9-[(4-METHOXY-3,5-DIMETHYLPYRIDIN-2-YL)METHYL]-9H-PURIN-2-AMINE'>94M</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&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tb10.26.1080 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=94M:6-CHLORO-9-[(4-METHOXY-3,5-DIMETHYLPYRIDIN-2-YL)METHYL]-9H-PURIN-2-AMINE'>94M</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=3o6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o6o OCA], [http://pdbe.org/3o6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o6o RCSB], [http://www.ebi.ac.uk/pdbsum/3o6o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o6o 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=3o6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o6o OCA], [https://pdbe.org/3o6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o6o RCSB], [https://www.ebi.ac.uk/pdbsum/3o6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o6o ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q389P1_TRYB2 Q389P1_TRYB2]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o6/3o6o_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o6/3o6o_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3o6o ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3o6o ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.
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Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design.,Pizarro JC, Hills T, Senisterra G, Wernimont AK, Mackenzie C, Norcross NR, Ferguson MA, Wyatt PG, Gilbert IH, Hui R PLoS Negl Trop Dis. 2013 Oct 17;7(10):e2492. doi: 10.1371/journal.pntd.0002492., eCollection 2013. PMID:24147171<ref>PMID:24147171</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 3o6o" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Heat Shock Protein structures|Heat Shock Protein structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Arrowsmith, C H]]
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[[Category: Large Structures]]
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[[Category: Bochkarev, A]]
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[[Category: Trypanosoma brucei]]
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[[Category: Bountra, C]]
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[[Category: Arrowsmith CH]]
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[[Category: Cossar, D]]
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[[Category: Bochkarev A]]
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[[Category: Edwards, A M]]
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[[Category: Bountra C]]
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[[Category: Fairlamb, A H]]
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[[Category: Cossar D]]
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[[Category: Ferguson, M A.J]]
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[[Category: Edwards AM]]
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[[Category: Hills, T]]
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[[Category: Fairlamb AH]]
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[[Category: Hui, R]]
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[[Category: Ferguson MAJ]]
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[[Category: Hutchinson, A]]
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[[Category: Hills T]]
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[[Category: Kozieradzki, I]]
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[[Category: Hui R]]
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[[Category: Li, Y]]
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[[Category: Hutchinson A]]
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[[Category: MacKenzie, C]]
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[[Category: Kozieradzki I]]
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[[Category: Pizarro, J C]]
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[[Category: Li Y]]
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[[Category: Structural genomic]]
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[[Category: MacKenzie C]]
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[[Category: Sullivan, H]]
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[[Category: Pizarro JC]]
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[[Category: Thompson, S]]
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[[Category: Sullivan H]]
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[[Category: Weadge, J]]
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[[Category: Thompson S]]
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[[Category: Weigelt, J]]
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[[Category: Weadge J]]
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[[Category: Wernimont, A K]]
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[[Category: Weigelt J]]
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[[Category: Wyatt, P]]
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[[Category: Wernimont AK]]
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[[Category: African sleeping sickness]]
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[[Category: Wyatt P]]
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[[Category: Chaperone]]
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[[Category: Heat shock protein]]
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[[Category: Sgc]]
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[[Category: Trypanosoma]]
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Current revision

Crystal Structure of the N-terminal domain of an HSP90 from Trypanosoma Brucei, Tb10.26.1080 in the presence of an the inhibitor BIIB021

PDB ID 3o6o

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