3fzf

From Proteopedia

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Revision as of 07:29, 5 December 2018

Crystal Structure of Hsc70/Bag1 in complex with ATP

Structural highlights

3fzf 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:	3fzh, 3fzk, 3fzl, 3fzm
Gene:	HSPA8, HSC70, HSP73, HSPA10 (HUMAN), BAG1, HAP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[2] ^[3] ^[4]

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^[5]

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

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
↑ Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimoto RI, Reed JC. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 1997 Aug 15;16(16):4887-96. PMID:9305631 doi:http://dx.doi.org/10.1093/emboj/16.16.4887
↑ Takayama S, Xie Z, Reed JC. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem. 1999 Jan 8;274(2):781-6. PMID:9873016
↑ Hung WJ, Roberson RS, Taft J, Wu DY. Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. Mol Cell Biol. 2003 May;23(10):3477-86. PMID:12724406
↑ 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

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/3fzf"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Hsc70/Bag1 in complex with ATP==
 <StructureSection load='3fzf' size='340' side='right' caption='[[3fzf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fzh|3fzh]], [[3fzk|3fzk]], [[3fzl|3fzl]], [[3fzm|3fzm]]</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 HUMAN]), BAG1, HAP ([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=3fzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fzf OCA], [http://pdbe.org/3fzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fzf RCSB], [http://www.ebi.ac.uk/pdbsum/3fzf 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=3fzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fzf OCA], [http://pdbe.org/3fzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fzf RCSB], [http://www.ebi.ac.uk/pdbsum/3fzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fzf ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fz/3fzf_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fz/3fzf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

3fzf

From Proteopedia

Revision as of 07:29, 5 December 2018

Crystal Structure of Hsc70/Bag1 in complex with ATP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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