3k97: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
Line 1: Line 1:


==HSP90 N-terminal domain in complex with 4-chloro-6-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diol==
==HSP90 N-terminal domain in complex with 4-chloro-6-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diol==
<StructureSection load='3k97' size='340' side='right' caption='[[3k97]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
<StructureSection load='3k97' size='340' side='right'caption='[[3k97]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3k97]] 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=3K97 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K97 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3k97]] 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=3K97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K97 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4CD:4-CHLORO-6-{[(2R)-2-(2-METHYLPHENYL)PYRROLIDIN-1-YL]CARBONYL}BENZENE-1,3-DIOL'>4CD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 1.95&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k98|3k98]], [[3k99|3k99]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CD:4-CHLORO-6-{[(2R)-2-(2-METHYLPHENYL)PYRROLIDIN-1-YL]CARBONYL}BENZENE-1,3-DIOL'>4CD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90, HSP90A, HSP90AA1, HSPC1, HSPCA ([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=3k97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k97 OCA], [https://pdbe.org/3k97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k97 RCSB], [https://www.ebi.ac.uk/pdbsum/3k97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k97 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=3k97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k97 OCA], [http://pdbe.org/3k97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k97 RCSB], [http://www.ebi.ac.uk/pdbsum/3k97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k97 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=3k97 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=3k97 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.
Dihydroxyphenylisoindoline amides as orally bioavailable inhibitors of the heat shock protein 90 (hsp90) molecular chaperone.,Kung PP, Huang B, Zhang G, Zhou JZ, Wang J, Digits JA, Skaptason J, Yamazaki S, Neul D, Zientek M, Elleraas J, Mehta P, Yin MJ, Hickey MJ, Gajiwala KS, Rodgers C, Davies JF, Gehring MR J Med Chem. 2010 Jan 14;53(1):499-503. PMID:19908836<ref>PMID:19908836</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3k97" 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: Gajiwala, K S]]
[[Category: Large Structures]]
[[Category: Acetylation]]
[[Category: Gajiwala KS]]
[[Category: Alternative splicing]]
[[Category: Atp binding domain]]
[[Category: Atp-binding]]
[[Category: Chaperone]]
[[Category: Cytoplasm]]
[[Category: Hsp90]]
[[Category: Inhibition]]
[[Category: N-terminal domain]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Stress response]]
Retrieved from "https://proteopedia.org/3k97"