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| | <StructureSection load='3fzf' size='340' side='right'caption='[[3fzf]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3fzf' size='340' side='right'caption='[[3fzf]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fzf]] is a 2 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=3FZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FZF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fzf]] 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=3FZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FZF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3fzh|3fzh]], [[3fzk|3fzk]], [[3fzl|3fzl]], [[3fzm|3fzm]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSPA8, HSC70, HSP73, HSPA10 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BAG1, HAP ([https://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=3fzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fzf OCA], [https://pdbe.org/3fzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fzf RCSB], [https://www.ebi.ac.uk/pdbsum/3fzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fzf 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=3fzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fzf OCA], [https://pdbe.org/3fzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fzf RCSB], [https://www.ebi.ac.uk/pdbsum/3fzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fzf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HSP7C_HUMAN HSP7C_HUMAN]] Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex.<ref>PMID:10722728</ref> [[https://www.uniprot.org/uniprot/BAG1_HUMAN BAG1_HUMAN]] Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli.<ref>PMID:9305631</ref> <ref>PMID:9873016</ref> <ref>PMID:12724406</ref>
| + | [https://www.uniprot.org/uniprot/HSP7C_HUMAN HSP7C_HUMAN] Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex.<ref>PMID:10722728</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dokurno, P]] | + | [[Category: Dokurno P]] |
| - | [[Category: Murray, J B]] | + | [[Category: Murray JB]] |
| - | [[Category: Surgenor, A E]] | + | [[Category: Surgenor AE]] |
| - | [[Category: Williamson, D S]] | + | [[Category: Williamson DS]] |
| - | [[Category: Adenosine]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Bag1]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Heat shock]]
| + | |
| - | [[Category: Hsc70]]
| + | |
| - | [[Category: Hsp70]]
| + | |
| - | [[Category: Nucleoside]]
| + | |
| - | [[Category: Nucleotide exchange factor]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Protein folding]]
| + | |
| - | [[Category: Small molecule inhibitor]]
| + | |
| - | [[Category: Stress response]]
| + | |
| Structural highlights
Function
HSP7C_HUMAN Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex.[1]
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 design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.
Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.,Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ J Med Chem. 2009 Mar 26;52(6):1510-3. PMID:19256508[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ, Shioda T. The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J Biol Chem. 2000 Mar 24;275(12):8825-34. PMID:10722728
- ↑ Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J Med Chem. 2009 Mar 26;52(6):1510-3. PMID:19256508 doi:10.1021/jm801627a
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