3k98

From Proteopedia

(Difference between revisions)

Revision as of 17:59, 8 February 2016

HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide

Structural highlights

3k98 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3k97, 3k99
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
↑ 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. Dihydroxyphenylisoindoline amides as orally bioavailable inhibitors of the heat shock protein 90 (hsp90) molecular chaperone. J Med Chem. 2010 Jan 14;53(1):499-503. PMID:19908836 doi:10.1021/jm901209q

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3k98"

@@ Line 2: / Line 2: @@
 <StructureSection load='3k98' size='340' side='right' caption='[[3k98]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3k98]] is a 2 chain structure with 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=3K98 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K98 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3k98]] is a 2 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=3K98 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k97|3k97]], [[3k99|3k99]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, 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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3k98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k98 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k98 RCSB], [http://www.ebi.ac.uk/pdbsum/3k98 PDBsum]</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=3k98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k98 OCA], [http://pdbe.org/3k98 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k98 RCSB], [http://www.ebi.ac.uk/pdbsum/3k98 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
     <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/chain_selection.php?pdb_ID=2ata 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="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3k98" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Gajiwala, K S]]
 [[Category: II, J F.Davies]]

3k98

From Proteopedia

Revision as of 17:59, 8 February 2016

HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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