4asb: Difference between revisions

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 <StructureSection load='4asb' size='340' side='right'caption='[[4asb]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4asb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ASB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ASB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4asb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ASB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ASB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8TO:(4E,6E,8S,9R,10E,12R,13R,14S,16R)-19-{[2-(DIMETHYLAMINO)ETHYL]AMINO}-13-HYDROXY-8,14-DIMETHOXY-4,10,12,16,21-PENTAMETHYL-3,20,22-TRIOXO-2-AZABICYCLO[16.3.1]DOCOSA-1(21),4,6,10,18-PENTAEN-9-YL+CARBAMATE'>8TO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.08&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a4h|1a4h]], [[1ah6|1ah6]], [[1ah8|1ah8]], [[1am1|1am1]], [[1amw|1amw]], [[1bgq|1bgq]], [[1hk7|1hk7]], [[1us7|1us7]], [[1usu|1usu]], [[1usv|1usv]], [[1zw9|1zw9]], [[1zwh|1zwh]], [[2akp|2akp]], [[2brc|2brc]], [[2bre|2bre]], [[2cg9|2cg9]], [[2cge|2cge]], [[2cgf|2cgf]], [[2iws|2iws]], [[2iwu|2iwu]], [[2iwx|2iwx]], [[2vw5|2vw5]], [[2vwc|2vwc]], [[2wep|2wep]], [[2weq|2weq]], [[2wer|2wer]], [[2xd6|2xd6]], [[2xx2|2xx2]], [[2xx4|2xx4]], [[2xx5|2xx5]], [[2yga|2yga]], [[2yge|2yge]], [[2ygf|2ygf]], [[4as9|4as9]], [[4asa|4asa]], [[4asf|4asf]], [[4asg|4asg]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8TO:(4E,6E,8S,9R,10E,12R,13R,14S,16R)-19-{[2-(DIMETHYLAMINO)ETHYL]AMINO}-13-HYDROXY-8,14-DIMETHOXY-4,10,12,16,21-PENTAMETHYL-3,20,22-TRIOXO-2-AZABICYCLO[16.3.1]DOCOSA-1(21),4,6,10,18-PENTAEN-9-YL+CARBAMATE'>8TO</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4asb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4asb OCA], [https://pdbe.org/4asb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4asb RCSB], [https://www.ebi.ac.uk/pdbsum/4asb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4asb ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/HSP82_YEAST HSP82_YEAST]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.<ref>PMID:17114002</ref>
+[https://www.uniprot.org/uniprot/HSP82_YEAST HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.<ref>PMID:17114002</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-The benzoquinone ansamycin geldanamycin and its derivatives are inhibitors of heat shock protein Hsp90, an emerging target for novel therapeutic agents both in cancer and in neurodegeneration. However, the toxicity of these compounds to normal cells has been ascribed to reaction with thiol nucleophiles at the quinone 19-position. We reasoned that blocking this position would ameliorate toxicity, and that it might also enforce a favourable conformational switch of the trans-amide group into the cis-form required for protein binding. Here, we report an efficient synthesis of such 19-substituted compounds and realization of our hypotheses. Protein crystallography established that the new compounds bind to Hsp90 with, as expected, a cis-amide conformation. Studies on Hsp90 inhibition in cells demonstrated the molecular signature of Hsp90 inhibitors: decreases in client proteins with compensatory increases in other heat shock proteins in both human breast cancer and dopaminergic neural cells, demonstrating their potential for use in the therapy of cancer or neurodegenerative diseases.
-Synthesis of 19-substituted geldanamycins with altered conformations and their binding to heat shock protein Hsp90.,Kitson RR, Chang CH, Xiong R, Williams HE, Davis AL, Lewis W, Dehn DL, Siegel D, Roe SM, Prodromou C, Ross D, Moody CJ Nat Chem. 2013 Apr;5(4):307-14. doi: 10.1038/nchem.1596. Epub 2013 Mar 10. PMID:23511419<ref>PMID:23511419</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4asb" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 17: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 18824]]
 [[Category: Large Structures]]
-[[Category: Prodromou, C]]
+[[Category: Saccharomyces cerevisiae]]
-[[Category: Roe, S M]]
+[[Category: Prodromou C]]
-[[Category: Ansamycin]]
+[[Category: Roe SM]]
-[[Category: Chaperone]]
-[[Category: Inhibition]]