1yc3: Difference between revisions

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New page: left|200px<br /> <applet load="1yc3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yc3, resolution 2.12Å" /> '''Crystal Structure o...
 
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[[Image:1yc3.gif|left|200px]]<br />
<applet load="1yc3" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1yc3, resolution 2.12&Aring;" />
'''Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''<br />


==Overview==
==Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles==
A series of dihydroxyphenylpyrazole compounds were identified as a unique, class of reversible Hsp90 inhibitors. The crystal structures for two of, the identified compounds complexed with the N-terminal ATP binding domain, of human Hsp90alpha were determined. The dihydroxyphenyl ring of the, compounds fits deeply into the adenine binding pocket with the C2 hydroxyl, group forming a direct hydrogen bond with the side chain of Asp93. The, pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the, hydroxyl group of Thr184 and to a water molecule, which is present in all, of the published HSP90 structures. One of the identified compounds (G3130), demonstrated cellular activities (in Her-2 degradation and activation of, Hsp70 promoter) consistent with the inhibition of cellular Hsp90, functions.
<StructureSection load='1yc3' size='340' side='right'caption='[[1yc3]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1yc3]] is a 1 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=1YC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YC3 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]] 2.12&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BC:4-(1,3-BENZODIOXOL-5-YL)-5-(5-ETHYL-2,4-DIHYDROXYPHENYL)-2H-PYRAZOLE-3-CARBOXYLIC+ACID'>4BC</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=1yc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc3 OCA], [https://pdbe.org/1yc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yc3 RCSB], [https://www.ebi.ac.uk/pdbsum/1yc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc3 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/yc/1yc3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1yc3 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1YC3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 4BC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YC3 OCA].
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 
== References ==
==Reference==
<references/>
Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles., Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ, Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15713410 15713410]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Brinker, A.]]
[[Category: Brinker A]]
[[Category: Caldwell, J.]]
[[Category: Caldwell J]]
[[Category: Choi, H.]]
[[Category: Choi H]]
[[Category: Gu, X.]]
[[Category: Gu X]]
[[Category: Han, S.]]
[[Category: Han S]]
[[Category: He, Y.]]
[[Category: He Y]]
[[Category: Kreusch, A.]]
[[Category: Kreusch A]]
[[Category: Lesley, S.A.]]
[[Category: Lesley SA]]
[[Category: Zhou, V.]]
[[Category: Zhou V]]
[[Category: 4BC]]
[[Category: cancer]]
[[Category: cell-cycle]]
[[Category: drug design]]
 
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Retrieved from "https://proteopedia.org/1yc3"