2mus: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2mus]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Podospora_anserina Podospora anserina]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MUS FirstGlance]. <br>
<table><tr><td colspan='2'>[[2mus]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Podospora_anserina Podospora anserina]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MUS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3LS:3,4-BIS(CARBOXYMETHYL)-2,2 5,2 5,2 5,2-QUINQUETHIOPHENE-5,5-DICARBOXYLIC+ACID'>3LS</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3LS:3,4-BIS(CARBOXYMETHYL)-2,2 5,2 5,2 5,2-QUINQUETHIOPHENE-5,5-DICARBOXYLIC+ACID'>3LS</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=2mus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mus OCA], [https://pdbe.org/2mus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mus RCSB], [https://www.ebi.ac.uk/pdbsum/2mus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mus ProSAT]</span></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=2mus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mus OCA], [https://pdbe.org/2mus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mus RCSB], [https://www.ebi.ac.uk/pdbsum/2mus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mus ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/HETS_PODAS HETS_PODAS] Responsible for heterokaryon incompatibility, a process that ensures that during spontaneous, vegetative cell fusion only compatible cells from the same colony survive (non-self-recognition). Forms a prion for the non-Mendelian trait [het-s]. Interacts with het-S from incompatible cells to trigger a lethal reaction that prevents the formation of viable heterokaryons. It is unknown if the native, soluble protein has a cellular function.<ref>PMID:1886611</ref> <ref>PMID:8224826</ref> <ref>PMID:9275200</ref>  
[https://www.uniprot.org/uniprot/HETS_PODAS HETS_PODAS] Responsible for heterokaryon incompatibility, a process that ensures that during spontaneous, vegetative cell fusion only compatible cells from the same colony survive (non-self-recognition). Forms a prion for the non-Mendelian trait [het-s]. Interacts with het-S from incompatible cells to trigger a lethal reaction that prevents the formation of viable heterokaryons. It is unknown if the native, soluble protein has a cellular function.<ref>PMID:1886611</ref> <ref>PMID:8224826</ref> <ref>PMID:9275200</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrP(Sc), a misfolded and aggregated form of the cellular prion protein (PrP(C)). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by &gt;80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.
Structure-based drug design identifies polythiophenes as antiprion compounds.,Herrmann US, Schutz AK, Shirani H, Huang D, Saban D, Nuvolone M, Li B, Ballmer B, Aslund AK, Mason JJ, Rushing E, Budka H, Nystrom S, Hammarstrom P, Bockmann A, Caflisch A, Meier BH, Nilsson KP, Hornemann S, Aguzzi A Sci Transl Med. 2015 Aug 5;7(299):299ra123. doi: 10.1126/scitranslmed.aab1923. PMID:26246168<ref>PMID:26246168</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mus" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 07:02, 1 May 2024

HADDOCK calculated model of LIN5001 bound to the HET-s amyloid

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