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| | ==Crystal structure of HSC70/BAG1 in complex with small molecule inhibitor== | | ==Crystal structure of HSC70/BAG1 in complex with small molecule inhibitor== |
| - | <StructureSection load='3m3z' size='340' side='right' caption='[[3m3z]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3m3z' size='340' side='right'caption='[[3m3z]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3m3z]] 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=3M3Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M3Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3m3z]] 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=3M3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M3Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3F5:5-O-(2-AMINO-2-OXOETHYL)-8-(METHYLAMINO)ADENOSINE'>3F5</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]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ldl|3ldl]], [[3ldn|3ldn]], [[3ldo|3ldo]], [[3ldp|3ldp]], [[3ldq|3ldq]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F5:5-O-(2-AMINO-2-OXOETHYL)-8-(METHYLAMINO)ADENOSINE'>3F5</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSPA8, HSC70, HSP73, HSPA10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BAG1, HAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3m3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3z OCA], [https://pdbe.org/3m3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m3z RCSB], [https://www.ebi.ac.uk/pdbsum/3m3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m3z ProSAT]</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=3m3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m3z RCSB], [http://www.ebi.ac.uk/pdbsum/3m3z PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3m3z" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[BAG protein|BAG protein]] | + | *[[BAG family proteins 3D structures|BAG family proteins 3D structures]] |
| - | *[[Heat Shock Proteins|Heat Shock Proteins]] | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Dokurno, P]] | + | [[Category: Large Structures]] |
| - | [[Category: Macias, A T]] | + | [[Category: Dokurno P]] |
| - | [[Category: Massey, A J]] | + | [[Category: Macias AT]] |
| - | [[Category: Shaw, T]] | + | [[Category: Massey AJ]] |
| - | [[Category: Surgenor, A E]] | + | [[Category: Shaw T]] |
| - | [[Category: Williamson, D S]] | + | [[Category: Surgenor AE]] |
| - | [[Category: Adenosine]]
| + | [[Category: Williamson DS]] |
| - | [[Category: Alternative initiation]]
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| - | [[Category: Apoptosis]]
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| - | [[Category: Atp-binding]]
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| - | [[Category: Chaperone]]
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| - | [[Category: Endoplasmatic reticulum]]
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| - | [[Category: Grp78]]
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| - | [[Category: Heat shock]]
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| - | [[Category: Host-virus interaction]]
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| - | [[Category: Hsc70]]
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| - | [[Category: Hsp70]]
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| - | [[Category: Nucleoside]]
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| - | [[Category: Nucleotide-binding]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Protein folding]]
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| - | [[Category: Selectivity]]
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| - | [[Category: Small molecule inhibitor]]
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| - | [[Category: Stress response]]
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| 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]
Publication Abstract from PubMed
78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.
Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity.,Macias AT, Williamson DS, Allen N, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Francis GL, Graham CJ, Howes R, Matassova N, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ J Med Chem. 2011 May 20. PMID:21526763[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
- ↑ Macias AT, Williamson DS, Allen N, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Francis GL, Graham CJ, Howes R, Matassova N, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ. Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity. J Med Chem. 2011 May 20. PMID:21526763 doi:10.1021/jm101625x
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