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4nh7

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Revision as of 07:20, 29 November 2017

Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity

Structural highlights

4nh7 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:	4nh8
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

HSP90 continues to be a target of interest for neurodegeneration indications. Selective knockdown of the HSP90 cytosolic isoforms alpha and beta is sufficient to reduce mutant huntingtin protein levels in vitro. Chemotype-dependent binding conformations of HSP90alpha/beta appear to strongly influence isoform selectivity. The rational design of HSP90alpha/beta inhibitors selective versus the mitochondrial (TRAP1) and endoplasmic reticulum (GRP94) isoforms offers a potential mitigating strategy for mechanism-based toxicities. Better tolerated HSP90 inhibitors would be attractive for targeting chronic neurodegenerative diseases such as Huntington's disease.

Correlation between chemotype-dependent binding conformations of HSP90alpha/beta and isoform selectivity-Implications for the structure-based design of HSP90alpha/beta selective inhibitors for treating neurodegenerative diseases.,Ernst JT, Liu M, Zuccola H, Neubert T, Beaumont K, Turnbull A, Kallel A, Vought B, Stamos D Bioorg Med Chem Lett. 2014 Jan 1;24(1):204-8. doi: 10.1016/j.bmcl.2013.11.036., Epub 2013 Nov 23. PMID:24332488^[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
↑ Ernst JT, Liu M, Zuccola H, Neubert T, Beaumont K, Turnbull A, Kallel A, Vought B, Stamos D. Correlation between chemotype-dependent binding conformations of HSP90alpha/beta and isoform selectivity-Implications for the structure-based design of HSP90alpha/beta selective inhibitors for treating neurodegenerative diseases. Bioorg Med Chem Lett. 2014 Jan 1;24(1):204-8. doi: 10.1016/j.bmcl.2013.11.036., Epub 2013 Nov 23. PMID:24332488 doi:http://dx.doi.org/10.1016/j.bmcl.2013.11.036

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nh7"

Categories: Human | Ernst, J | Zuccola, H J | A/b fold | Chaperone

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4nh7]] 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=4NH7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NH7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HIE:4-[6,6-DIMETHYL-4-OXO-3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOL-1-YL]-2-[(CIS-4-HYDROXYCYCLOHEXYL)AMINO]BENZAMIDE'>HIE</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E0G:4-[6,6-dimethyl-4-oxidanylidene-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-oxidanylcyclohexyl)amino]benzamide'>E0G</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nh8|4nh8]]</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>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4nh7" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Heat Shock Proteins|Heat Shock Proteins]]
 == References ==
 <references/>

4nh7

From Proteopedia

Revision as of 07:20, 29 November 2017

Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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