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3ldq

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Revision as of 20:44, 25 December 2014

Crystal structure of HSC70/BAG1 in complex with small molecule inhibitor

Structural highlights

3ldq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3ldl, 3ldn, 3ldo, 3ldp
Gene:	HSPA8, HSC70, HSP73, HSPA10 (Homo sapiens), BAG1, HAP (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

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^[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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ldq"

@@ Line 8: / Line 8: @@
 <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=3ldq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ldq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ldq RCSB], [http://www.ebi.ac.uk/pdbsum/3ldq PDBsum]</span></td></tr>
 </table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3ldq

From Proteopedia

Revision as of 20:44, 25 December 2014

Crystal structure of HSC70/BAG1 in complex with small molecule inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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