2bz5: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2bz5.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_2bz5", 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_2bz5|  PDB=2bz5  |  SCENE=  }}
'''STRUCTURE-BASED DISCOVERY OF A NEW CLASS OF HSP90 INHIBITORS'''


==Structure-based Discovery of a New Class of Hsp90 Inhibitors==
<StructureSection load='2bz5' size='340' side='right'caption='[[2bz5]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== 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.


==Overview==
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>
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.


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


==Reference==
==See Also==
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]
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[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]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:00:06 2008''
Retrieved from "https://proteopedia.org/2bz5"