2bz5: Difference between revisions

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[[Image:2bz5.gif|left|200px]]


{{Structure
==Structure-based Discovery of a New Class of Hsp90 Inhibitors==
|PDB= 2bz5 |SIZE=350|CAPTION= <scene name='initialview01'>2bz5</scene>, resolution 1.90&Aring;
<StructureSection load='2bz5' size='340' side='right'caption='[[2bz5]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Ab4+Binding+Site+For+Chain+B'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=AB4:2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE'>AB4</scene>
<table><tr><td colspan='2'>[[2bz5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZ5 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AB4:2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE'>AB4</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bz5 OCA], [https://pdbe.org/2bz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2bz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bz5 ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bz5 OCA], [http://www.ebi.ac.uk/pdbsum/2bz5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bz5 RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bz/2bz5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2bz5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Docking-based virtual screening identified 1-(2-phenol)-2-naphthol compounds as a new class of Hsp90 inhibitors of low to sub-micromolar potency. Here we report the binding affinities and cellular activities of several members of this class. A high resolution crystal structure of the most potent compound reveals its binding mode in the ATP binding site of Hsp90, providing a rationale for the observed activity of the series and suggesting strategies for developing compounds with improved properties.


'''STRUCTURE-BASED DISCOVERY OF A NEW CLASS OF HSP90 INHIBITORS'''
Structure-based discovery of a new class of Hsp90 inhibitors.,Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L Bioorg Med Chem Lett. 2005 Dec 1;15(23):5187-91. Epub 2005 Oct 3. PMID:16202589<ref>PMID:16202589</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2bz5" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
Docking-based virtual screening identified 1-(2-phenol)-2-naphthol compounds as a new class of Hsp90 inhibitors of low to sub-micromolar potency. Here we report the binding affinities and cellular activities of several members of this class. A high resolution crystal structure of the most potent compound reveals its binding mode in the ATP binding site of Hsp90, providing a rationale for the observed activity of the series and suggesting strategies for developing compounds with improved properties.
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 
== References ==
==About this Structure==
<references/>
2BZ5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZ5 OCA].
__TOC__
 
</StructureSection>
==Reference==
Structure-based discovery of a new class of Hsp90 inhibitors., Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L, Bioorg Med Chem Lett. 2005 Dec 1;15(23):5187-91. Epub 2005 Oct 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16202589 16202589]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Barril, X.]]
[[Category: Barril X]]
[[Category: Brough, P.]]
[[Category: Brough P]]
[[Category: Drysdale, M.]]
[[Category: Drysdale M]]
[[Category: Hubbard, R E.]]
[[Category: Hubbard RE]]
[[Category: Massey, A.]]
[[Category: Massey A]]
[[Category: Surgenor, A.]]
[[Category: Surgenor A]]
[[Category: Wright, L.]]
[[Category: Wright L]]
[[Category: atp-binding]]
[[Category: chaperone]]
[[Category: heat shock]]
[[Category: nucleotide-binding]]
[[Category: phosphorylation]]
 
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Retrieved from "https://proteopedia.org/2bz5"