3hhu

<StructureSection load='3hhu' size='340' side='right' caption='[[3hhu]], [[Resolution|resolution]] 1.59&Aring;' scene=''>

<table><tr><td colspan='2'>[[3hhu]] 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1byq|1byq]], [[1osf|1osf]], [[1uy6|1uy6]], [[1yc1|1yc1]], [[1yet|1yet]], [[2bsm|2bsm]], [[2bto|2bto]], [[2byi|2byi]], [[2c2l|2c2l]], [[2cct|2cct]], [[2ccu|2ccu]]</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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://pdbe.org/3hhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/3hhu_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

Heat-shock protein-90 is an attractive target for anticancer drugs, as heat-shock protein-90 blockers such as the ansamycin 17-(allylamino)-17-demethoxygeldanamycin greatly reduce the expression of many signaling molecules that are disregulated in cancer cells and are key drivers of tumor growth and metastasis. While 17-(allylamino)-17-demethoxygeldanamycin has shown promise in clinical trials, this compound class has significant template-related drawbacks. In this paper, we describe a new, potent non-ansamycin small-molecule inhibitor of heat-shock protein-90, BX-2819, containing resorcinol and triazolothione rings. Structural studies demonstrate binding of BX-2819 to the ADP/ATP-binding pocket of heat-shock protein-90. The compound blocked expression of heat-shock protein-90 client proteins in cancer cell lines and inhibited cell growth with a potency similar to 17-(allylamino)-17-demethoxygeldanamycin. In a panel of four cancer cell lines, BX-2819 blocked growth with an average IC(50) value of 32 nM (range of 7-72 nM). Efficacy studies demonstrated that treatment with BX-2819 significantly inhibited the growth of NCI-N87 and HT-29 tumors in nude mice, consistent with pharmacodynamic studies showing inhibition of heat-shock protein-90 client protein expression in tumors for greater than 16 h after dosing. These data support further studies to assess the potential of BX-2819 and related analogs for the treatment of cancer.

 

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[[Category: Adler, M]]

[[Category: Whitlow, M]]

[[Category: Alternative splicing]]

[[Category: Stress response]]