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| | <StructureSection load='7lt0' size='340' side='right'caption='[[7lt0]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='7lt0' size='340' side='right'caption='[[7lt0]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7lt0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LT0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7lt0]] 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=7LT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LT0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ONJ:(1,3-dihydro-2H-isoindol-2-yl){3-[(3,4-dimethylphenyl)sulfanyl]-4-hydroxyphenyl}methanone'>ONJ</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]] 1.697Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ONJ:(1,3-dihydro-2H-isoindol-2-yl){3-[(3,4-dimethylphenyl)sulfanyl]-4-hydroxyphenyl}methanone'>ONJ</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-chaperonin_molecular_chaperone_ATPase Non-chaperonin molecular chaperone ATPase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.10 3.6.4.10] </span></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=7lt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lt0 OCA], [https://pdbe.org/7lt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lt0 RCSB], [https://www.ebi.ac.uk/pdbsum/7lt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lt0 ProSAT]</span></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=7lt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lt0 OCA], [https://pdbe.org/7lt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lt0 RCSB], [https://www.ebi.ac.uk/pdbsum/7lt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lt0 ProSAT]</span></td></tr> |
| | </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>
| + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 7lt0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7lt0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-chaperonin molecular chaperone ATPase]]
| + | [[Category: Balch M]] |
| - | [[Category: Balch, M]] | + | [[Category: Deng J]] |
| - | [[Category: Deng, J]] | + | [[Category: Matts R]] |
| - | [[Category: Matts, R]] | + | [[Category: Peng S]] |
| - | [[Category: Peng, S]] | + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Hsp90]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
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
The 90 kDa heat shock protein (Hsp90) is a molecular chaperone that processes nascent polypeptides into their biologically active conformations. Many of these proteins contribute to the progression of cancer, and consequently, inhibition of the Hsp90 protein folding machinery represents an innovative approach toward cancer chemotherapy. However, clinical trials with Hsp90 N-terminal inhibitors have encountered deleterious side effects and toxicities, which appear to result from the pan -inhibition of all four Hsp90 isoforms. Therefore, the development of isoform-selective Hsp90 inhibitors is sought to delineate the pathological role played by each isoform. Herein, we describe a structure-based approach that was used to design the first Hsp90a-selective inhibitors, which exhibit > 50-fold selectivity versus other Hsp90 isoforms.
Selective Inhibition of the Hsp90a isoform.,Blagg B, Mishra S, Khandelwal A, Bannerjee M, Balch M, Peng S, Davis R, Merfeld T, Menthali V, Deng J, Matts R Angew Chem Int Ed Engl. 2021 Feb 23. doi: 10.1002/anie.202015422. PMID:33621416[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Blagg B, Mishra S, Khandelwal A, Bannerjee M, Balch M, Peng S, Davis R, Merfeld T, Menthali V, Deng J, Matts R. Selective Inhibition of the Hsp90a isoform. Angew Chem Int Ed Engl. 2021 Feb 23. doi: 10.1002/anie.202015422. PMID:33621416 doi:http://dx.doi.org/10.1002/anie.202015422
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