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2kgp

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==Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by Novantrone (Mitoxantrone)==
==Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by Novantrone (Mitoxantrone)==
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<StructureSection load='2kgp' size='340' side='right' caption='[[2kgp]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
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<StructureSection load='2kgp' size='340' side='right'caption='[[2kgp]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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[[2kgp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGP OCA]. <br>
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<table><tr><td colspan='2'>[[2kgp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KGP FirstGlance]. <br>
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<b>[[Ligand|Ligands:]]</b> <scene name='pdbligand=MIX:1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE'>MIX</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MIX:1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE'>MIX</scene></td></tr>
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<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kgp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kgp RCSB], [http://www.ebi.ac.uk/pdbsum/2kgp PDBsum]</span><br>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kgp OCA], [https://pdbe.org/2kgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kgp RCSB], [https://www.ebi.ac.uk/pdbsum/2kgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kgp ProSAT]</span></td></tr>
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== Publication Abstract from PubMed ==
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</table>
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Some familial neurodegenerative diseases are associated with mutations that destabilize a putative stem-loop structure within an intronic region of the tau pre-messenger RNA (mRNA) and alter the production of tau protein isoforms by alternative splicing. Because stabilization of the stem loop reverses the splicing pattern associated with neurodegeneration, small molecules that stabilize this stem loop would provide new ways to dissect the mechanism of neurodegeneration and treat tauopathies. The anticancer drug mitoxantrone was recently identified in a high throughput screen to stabilize the tau pre-mRNA stem loop. Here we report the solution structure of the tau mRNA-mitoxantrone complex, validated by the structure-activity relationship of existing mitoxantrone analogs. The structure describes the molecular basis for their interaction with RNA and provides a rational basis to optimize the activity of this new class of RNA-binding molecules.
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Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by novantrone (mitoxantrone).,Zheng S, Chen Y, Donahue CP, Wolfe MS, Varani G Chem Biol. 2009 May 29;16(5):557-66. PMID:19477420<ref>PMID:19477420</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Chen, Y.]]
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[[Category: Large Structures]]
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[[Category: Donahue, C P.]]
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[[Category: Chen Y]]
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[[Category: Varani, G.]]
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[[Category: Donahue CP]]
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[[Category: Wolfe, M S.]]
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[[Category: Varani G]]
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[[Category: Zheng, S.]]
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[[Category: Wolfe MS]]
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[[Category: Mitoxantrone]]
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[[Category: Zheng S]]
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[[Category: Novantrone]]
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[[Category: Rna]]
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[[Category: Rna-small molecule]]
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[[Category: Splicing regulatory element]]
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[[Category: Tau pre-mrna]]
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[[Category: Tauopathy]]
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Current revision

Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by Novantrone (Mitoxantrone)

PDB ID 2kgp

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