4io8
From Proteopedia
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| - | + | ==Crystal structure of human HSP70 complexed with 4-{(2R,3S,4R)-5-[(R)-6-Amino-8-(3,4-dichloro-benzylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxymethyl}-benzonitrile== | |
| - | + | <StructureSection load='4io8' size='340' side='right' caption='[[4io8]], [[Resolution|resolution]] 2.58Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4io8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IO8 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FD:4-[[(2R,3S,4R,5R)-5-[6-AMINO-8-[(3,4-DICHLOROPHENYL)METHYLAMINO]PURIN-9-YL]-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXYMETHYL]BENZONITRILE'>3FD</scene></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=4io8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4io8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4io8 RCSB], [http://www.ebi.ac.uk/pdbsum/4io8 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The molecular chaperones of the Hsp70 family have been recognized as targets for anti-cancer therapy. Since several paralogs of Hsp70 proteins exist in cytosol, endoplasmic reticulum and mitochondria, we investigated which isoform needs to be down-regulated for reducing viability of cancer cells. For two recently identified small molecule inhibitors, VER-155008 and 2-phenylethynesulfonamide (PES), which are proposed to target different sites in Hsp70s, we analyzed the molecular mode of action in vitro. We found that for significant reduction of viability of cancer cells simultaneous knockdown of heat-inducible Hsp70 (HSPA1) and constitutive Hsc70 (HSPA8) is necessary. The compound VER-155008, which binds to the nucleotide binding site of Hsp70, arrests the nucleotide binding domain (NBD) in a half-open conformation and thereby acts as ATP-competitive inhibitor that prevents allosteric control between NBD and substrate binding domain (SBD). Compound PES interacts with the SBD of Hsp70 in an unspecific, detergent-like fashion, under the conditions tested. None of the two inhibitors investigated was isoform-specific. | ||
| - | + | Functional analysis of hsp70 inhibitors.,Schlecht R, Scholz SR, Dahmen H, Wegener A, Sirrenberg C, Musil D, Bomke J, Eggenweiler HM, Mayer MP, Bukau B PLoS One. 2013 Nov 12;8(11):e78443. doi: 10.1371/journal.pone.0078443. PMID:24265689<ref>PMID:24265689</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Musil, D | + | |
| - | [[Category: Scholz, S | + | ==See Also== |
| + | *[[Beta-ketoacyl-ACP reductase|Beta-ketoacyl-ACP reductase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Musil, D]] | ||
| + | [[Category: Scholz, S]] | ||
[[Category: Atpase]] | [[Category: Atpase]] | ||
[[Category: Chaperone]] | [[Category: Chaperone]] | ||
[[Category: Hsp70]] | [[Category: Hsp70]] | ||
[[Category: Molecular chaperone]] | [[Category: Molecular chaperone]] | ||
Revision as of 16:36, 21 December 2014
Crystal structure of human HSP70 complexed with 4-{(2R,3S,4R)-5-[(R)-6-Amino-8-(3,4-dichloro-benzylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxymethyl}-benzonitrile
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Categories: Human | Musil, D | Scholz, S | Atpase | Chaperone | Hsp70 | Molecular chaperone
