3k98
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide== | ==HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide== | ||
| - | <StructureSection load='3k98' size='340' side='right' caption='[[3k98]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3k98' size='340' side='right'caption='[[3k98]], [[Resolution|resolution]] 2.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3k98]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3k98]] 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=3K98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K98 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RC:(1R)-2-[(5-CHLORO-2,4-DIHYDROXYPHENYL)CARBONYL]-N-ETHYL-2,3-DIHYDRO-1H-ISOINDOLE-1-CARBOXAMIDE'>1RC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1RC:(1R)-2-[(5-CHLORO-2,4-DIHYDROXYPHENYL)CARBONYL]-N-ETHYL-2,3-DIHYDRO-1H-ISOINDOLE-1-CARBOXAMIDE'>1RC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3k98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k98 OCA], [https://pdbe.org/3k98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k98 RCSB], [https://www.ebi.ac.uk/pdbsum/3k98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k98 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k9/3k98_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k9/3k98_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 20: | 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=3k98 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=3k98 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3k98" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Heat Shock | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: II | + | [[Category: Davies II JF]] |
| - | [[Category: | + | [[Category: Gajiwala KS]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide
| |||||||||||
