View source for 7upg


==Tau Paired Helical Filament from Alzheimer's Disease incubated with EGCG for 3 hours==
<StructureSection load='7upg' size='340' side='right'caption='[[7upg]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7upg]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UPG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KDH:(2R,3R)-5,7-DIHYDROXY-2-(3,4,5-TRIHYDROXYPHENYL)-3,4-DIHYDRO-2H-CHROMEN-3-YL+3,4,5-TRIHYDROXYBENZOATE'>KDH</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=7upg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7upg OCA], [https://pdbe.org/7upg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7upg RCSB], [https://www.ebi.ac.uk/pdbsum/7upg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7upg ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Alzheimer's disease (AD) is the consequence of neuronal death and brain atrophy associated with the aggregation of protein tau into fibrils. Thus disaggregation of tau fibrils could be a therapeutic approach to AD. The small molecule EGCG, abundant in green tea, has long been known to disaggregate tau and other amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain. Here we have cryogenically trapped an intermediate of brain-extracted tau fibrils on the kinetic pathway to EGCG-induced disaggregation and have determined its cryoEM structure. The structure reveals that EGCG molecules stack in polar clefts between the paired helical protofilaments that pathologically define AD. Treating the EGCG binding position as a pharmacophore, we computationally screened thousands of drug-like compounds for compatibility for the pharmacophore, discovering several that experimentally disaggregate brain-derived tau fibrils in vitro. This work suggests the potential of structure-based, small-molecule drug discovery for amyloid diseases.

Structure-based discovery of small molecules that disaggregate Alzheimer's disease tissue derived tau fibrils in vitro.,Seidler PM, Murray KA, Boyer DR, Ge P, Sawaya MR, Hu CJ, Cheng X, Abskharon R, Pan H, DeTure MA, Williams CK, Dickson DW, Vinters HV, Eisenberg DS Nat Commun. 2022 Sep 16;13(1):5451. doi: 10.1038/s41467-022-32951-4. PMID:36114178<ref>PMID:36114178</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7upg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boyer DR]]
[[Category: Eisenberg DS]]
[[Category: Ge P]]
[[Category: Murray KA]]
[[Category: Sawaya MR]]
[[Category: Seidler PM]]