6dr4: Difference between revisions

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-'''Unreleased structure'''
-The entry 6dr4 is ON HOLD  until Paper Publication
+==X-ray crystallographic structure of a covalent trimer derived from A-beta 17_36 containing the I31V point mutation==
+<StructureSection load='6dr4' size='340' side='right' caption='[[6dr4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6dr4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DR4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DR4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=6dr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dr4 OCA], [http://pdbe.org/6dr4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dr4 RCSB], [http://www.ebi.ac.uk/pdbsum/6dr4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dr4 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Soluble oligomers of the beta-amyloid peptide, Abeta, are associated with the progression of Alzheimer's disease. Although many small molecules bind to these assemblies, the details of how these molecules interact with Abeta oligomers remain unknown. This paper reports that crystal violet, and other C3 symmetric triphenylmethane dyes, bind to C3 symmetric trimers derived from Abeta17-36. Binding changes the color of the dyes from purple to blue, and causes them to fluoresce red when irradiated with green light. Job plot and analytical ultracentrifugation experiments reveal that two trimers complex with one dye molecule. Studies with several triphenylmethane dyes reveal that three N, N-dialkylamino substituents are required for complexation. Several mutant trimers, in which Phe19, Phe20, and Ile31 were mutated to cyclohexylalanine, valine, and cyclohexylglycine, were prepared to probe the triphenylmethane dye binding site. Size exclusion chromatography, SDS-PAGE, and X-ray crystallographic studies demonstrate that these mutations do not impact the structure or assembly of the triangular trimer. Fluorescence spectroscopy and analytical ultracentrifugation experiments reveal that the dye packs against an aromatic surface formed by the Phe20 side chains and is clasped by the Ile31 side chains. Docking and molecular modeling provide a working model of the complex in which the triphenylmethane dye is sandwiched between two triangular trimers. Collectively, these findings demonstrate that the X-ray crystallographic structures of triangular trimers derived from Abeta can be used to guide the discovery of ligands that bind to soluble oligomers derived from Abeta.
-Authors: Salveson, P.J., Nowick, J.S.
+Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Abeta.,Salveson PJ, Haerianardakani S, Thuy-Boun A, Yoo S, Kreutzer AG, Demeler B, Nowick JS J Am Chem Soc. 2018 Sep 19;140(37):11745-11754. doi: 10.1021/jacs.8b06568. Epub, 2018 Sep 6. PMID:30125493<ref>PMID:30125493</ref>
-Description: X-ray crystallographic structure of a covalent trimer derived from A-beta 17_36 containing the I31V point mutation
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Salveson, P.J]]
+<div class="pdbe-citations 6dr4" style="background-color:#fffaf0;"></div>
-[[Category: Nowick, J.S]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Nowick, J S]]
+[[Category: Salveson, P J]]
+[[Category: Abeta]]
+[[Category: Alzheimers disease]]
+[[Category: Amyloid]]
+[[Category: De novo protein]]
+[[Category: Oligomer]]