2kgp
From Proteopedia
(Difference between revisions)
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<StructureSection load='2kgp' size='340' side='right' caption='[[2kgp]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | <StructureSection load='2kgp' size='340' side='right' caption='[[2kgp]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2kgp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGP OCA]. <br> | + | <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]. <br> |
| - | <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> | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIX:1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE'>MIX</scene><br> |
| - | <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>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> |
| - | <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>< | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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. | 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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:59, 1 May 2014
Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by Novantrone (Mitoxantrone)
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