4h5n

From Proteopedia

(Difference between revisions)

Revision as of 14:50, 11 August 2016

HSC70 NBD with PO4, Na, Cl

Structural highlights

4h5n 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:	4h5r, 4h5t, 4h5v, 4h5w
Gene:	HSC70, HSP73, HSPA10, HSPA8 (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]

Publication Abstract from PubMed

In recent years the chaperone HSC-70 has become a target for drug design with a strong focus in anticancer therapies. In our study of possible inhibitors of HSC-70 enzymatic activity we screened compounds by NMR as well as X-ray crystallography. As part of our screening efforts we crystallized the human HSC-70 ATP binding domain and obtained novel crystal forms in addition to known structures. The new crystal structures highlight the mobility of the entire domain previously described by NMR, which was linked to its chaperone activity but not yet demonstrated by X-ray crystallography. Conformational changes across the entire molecule have been elucidated in response to the binding of small molecule ligands and show a pattern of mobility consistent with postulated signal transduction modes between the nucleotide binding domain (NBD) and the substrate binding domain (SBD). In addition, two crystal structures contained glycerol bound at a new site. Binding studies performed with glycerol analogs proved inhibitory properties of the site, which were further characterized by isothermal calorimetry and in silico docking studies. The presence of two binding pockets enabled us to explore a novel method of inhibition by compounds that bridge the adjacent phosphate and glycerol binding sites. Finally, an example of such a bridged inhibitor is proposed.

New crystal structures of HSC-70 ATP binding domain confirm the role of individual binding pockets and suggests a new method of inhibition.,Zhang Z, Cellitti J, Teriete P, Pellecchia M, Stec B Biochimie. 2014 Nov 27. pii: S0300-9084(14)00353-8. doi:, 10.1016/j.biochi.2014.11.012. PMID:25433210^[2]

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
↑ Zhang Z, Cellitti J, Teriete P, Pellecchia M, Stec B. New crystal structures of HSC-70 ATP binding domain confirm the role of individual binding pockets and suggests a new method of inhibition. Biochimie. 2014 Nov 27. pii: S0300-9084(14)00353-8. doi:, 10.1016/j.biochi.2014.11.012. PMID:25433210 doi:http://dx.doi.org/10.1016/j.biochi.2014.11.012

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4h5n"

Categories: Human | Stec, B | Nucleotide binding domain | Transcription

@@ Line 1: / Line 1: @@
 ==HSC70 NBD with PO4, Na, Cl==
 <StructureSection load='4h5n' size='340' side='right' caption='[[4h5n]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4h5r|4h5r]], [[4h5t|4h5t]], [[4h5v|4h5v]], [[4h5w|4h5w]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSC70, HSP73, HSPA10, HSPA8 ([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=4h5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h5n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h5n RCSB], [http://www.ebi.ac.uk/pdbsum/4h5n 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=4h5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h5n OCA], [http://pdbe.org/4h5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h5n RCSB], [http://www.ebi.ac.uk/pdbsum/4h5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h5n ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4h5n" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4h5n

From Proteopedia

Revision as of 14:50, 11 August 2016

HSC70 NBD with PO4, Na, Cl

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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