2yge: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2yge.png|left|200px]]
+==E88G-N92L Mutant of N-Term HSP90 complexed with Geldanamycin==
+<StructureSection load='2yge' size='340' side='right' caption='[[2yge]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2yge]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YGE FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDM:GELDANAMYCIN'>GDM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hk7|1hk7]], [[2xx5|2xx5]], [[1a4h|1a4h]], [[1us7|1us7]], [[2bre|2bre]], [[2vwc|2vwc]], [[2cg9|2cg9]], [[2xd6|2xd6]], [[1ah6|1ah6]], [[1bgq|1bgq]], [[1usv|1usv]], [[2iws|2iws]], [[2wer|2wer]], [[1amw|1amw]], [[1usu|1usu]], [[2brc|2brc]], [[1zwh|1zwh]], [[2vw5|2vw5]], [[2weq|2weq]], [[1ah8|1ah8]], [[2cgf|2cgf]], [[2xx4|2xx4]], [[2xx2|2xx2]], [[2iwu|2iwu]], [[1am1|1am1]], [[2cge|2cge]], [[2iwx|2iwx]], [[2wep|2wep]], [[2akp|2akp]], [[1zw9|1zw9]], [[2yga|2yga]], [[2ygf|2ygf]]</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=2yge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yge OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yge RCSB], [http://www.ebi.ac.uk/pdbsum/2yge PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Much attention is focused on the benzoquinone ansamycins as anticancer agents, with several derivatives of the natural product geldanamycin (GdA) now in clinical trials. These drugs are selective inhibitors of Hsp90, a molecular chaperone vital for many of the activities that drive cancer progression. Mutational changes to their interaction site, the extremely conserved ATP binding site of Hsp90, would mostly be predicted to inactivate the chaperone. As a result, drug resistance should not arise readily this way. Nevertheless, Streptomyces hygroscopicus, the actinomycete that produces GdA, has evolved an Hsp90 family protein (HtpG) that lacks GdA binding. It is altered in certain of the highly conserved amino acids making contacts to this antibiotic in crystal structures of GdA bound to eukaryotic forms of Hsp90. Two of these amino acid changes, located on one side of the nucleotide-binding cleft, weakened GdA/Hsp90 binding and conferred partial GdA resistance when inserted into the endogenous Hsp90 of yeast cells. Crystal structures revealed their main effect to be a weakening of interactions with the C-12 methoxy group of the GdA ansamycin ring. This is the first study to demonstrate that partial GdA resistance is possible by mutation within the ATP binding pocket of Hsp90.-Millson, S. H., Chua, C.-S., Roe, S. M., Polier, S., Solovieva, S., Pearl, L. H., Sim, T.-S., Prodromou, C., Piper, P. W. Features of the Streptomyces hygroscopicus HtpG reveal how partial geldanamycin resistance can arise with mutation to the ATP binding pocket of a eukaryotic Hsp90.
-{{STRUCTURE_2yge|  PDB=2yge  |  SCENE=  }}
+Features of the Streptomyces hygroscopicus HtpG reveal how partial geldanamycin resistance can arise with mutation to the ATP binding pocket of a eukaryotic Hsp90.,Millson SH, Chua CS, Roe SM, Polier S, Solovieva S, Pearl LH, Sim TS, Prodromou C, Piper PW FASEB J. 2011 Nov;25(11):3828-37. Epub 2011 Jul 21. PMID:21778327<ref>PMID:21778327</ref>
-===E88G-N92L Mutant of N-Term HSP90 complexed with Geldanamycin===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_21778327}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[2yge]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YGE OCA].
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:021778327</ref><references group="xtra"/>
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Pearl, L H.]]
+[[Category: Pearl, L H]]
-[[Category: Prodromou, C.]]
+[[Category: Prodromou, C]]
-[[Category: Roe, M.]]
+[[Category: Roe, M]]
 [[Category: Chaperone]]