1yc4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:56, 14 February 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
==Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles==
==Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles==
-
<StructureSection load='1yc4' size='340' side='right' caption='[[1yc4]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
+
<StructureSection load='1yc4' size='340' side='right'caption='[[1yc4]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[1yc4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YC4 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[1yc4]] 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=1YC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YC4 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43P:4-(1H-IMIDAZOL-4-YL)-3-(5-ETHYL-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE'>43P</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yc1|1yc1]], [[1yc3|1yc3]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43P:4-(1H-IMIDAZOL-4-YL)-3-(5-ETHYL-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE'>43P</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSPCA, HSP90A, HSPC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1yc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc4 OCA], [https://pdbe.org/1yc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yc4 RCSB], [https://www.ebi.ac.uk/pdbsum/1yc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc4 ProSAT]</span></td></tr>
-
<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=1yc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc4 OCA], [http://pdbe.org/1yc4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yc4 RCSB], [http://www.ebi.ac.uk/pdbsum/1yc4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc4 ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://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>
+
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 21: Line 20:
</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=1yc4 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=1yc4 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
-
<div style="background-color:#fffaf0;">
 
-
== Publication Abstract from PubMed ==
 
-
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.
 
- 
-
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:15713410<ref>PMID:15713410</ref>
 
- 
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
-
</div>
 
-
<div class="pdbe-citations 1yc4" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
-
*[[Heat Shock Proteins|Heat Shock Proteins]]
+
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
-
[[Category: Brinker, A]]
+
[[Category: Large Structures]]
-
[[Category: Caldwell, J]]
+
[[Category: Brinker A]]
-
[[Category: Choi, H]]
+
[[Category: Caldwell J]]
-
[[Category: Gu, X]]
+
[[Category: Choi H]]
-
[[Category: Han, S]]
+
[[Category: Gu X]]
-
[[Category: He, Y]]
+
[[Category: Han S]]
-
[[Category: Kreusch, A]]
+
[[Category: He Y]]
-
[[Category: Lesley, S A]]
+
[[Category: Kreusch A]]
-
[[Category: Zhou, V]]
+
[[Category: Lesley SA]]
-
[[Category: Cancer]]
+
[[Category: Zhou V]]
-
[[Category: Cell cycle]]
+
-
[[Category: Cell-cycle]]
+
-
[[Category: Drug design]]
+

Current revision

Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles

PDB ID 1yc4

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools