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| - | [[Image:1ei2.gif|left|200px]] | |
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| - | <!--
| + | ==STRUCTURAL BASIS FOR RECOGNITION OF THE RNA MAJOR GROOVE IN THE TAU EXON 10 SPLICING REGULATORY ELEMENT BY AMINOGLYCOSIDE ANTIBIOTICS== |
| - | The line below this paragraph, containing "STRUCTURE_1ei2", creates the "Structure Box" on the page.
| + | <StructureSection load='1ei2' size='340' side='right'caption='[[1ei2]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1ei2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EI2 FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </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=NMY:NEOMYCIN'>NMY</scene></td></tr> |
| - | {{STRUCTURE_1ei2| PDB=1ei2 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ei2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ei2 OCA], [https://pdbe.org/1ei2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ei2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ei2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ei2 ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''STRUCTURAL BASIS FOR RECOGNITION OF THE RNA MAJOR GROOVE IN THE TAU EXON 10 SPLICING REGULATORY ELEMENT BY AMINOGLYCOSIDE ANTIBIOTICS'''
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | | + | [[Category: Homo sapiens]] |
| - | ==Overview== | + | [[Category: Large Structures]] |
| - | Drug-like molecules that bind RNA with sequence selectivity would provide valuable tools to elucidate gene expression pathways and new avenues to the treatment of degenerative and chronic conditions. Efforts at discovering such agents have been hampered, until recently, by the limited knowledge of RNA recognition principles. Several recent structures of aminoglycoside-RNA complexes have begun to reveal the structural basis for RNA-drug recognition. However, the absence of suitable chemical scaffolds known to bind the RNA major groove, where specificity could be provided by the diversity of functional groups exposed on the RNA bases, has represented a major obstacle. Here we report an investigation of the structural basis for recognition of an RNA stem-loop by neomycin, a naturally occurring aminoglycoside antibiotic. We found that neomycin binds the RNA stem-loop that regulates alternative splicing of exon 10 within the gene coding for human tau protein. Mutations within this splicing regulatory element destabilise the RNA structure and cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an autosomal dominant condition leading to neurodegeneration and death. The three-dimensional structure of the RNA-neomycin complex shows interaction of the drug in the major groove of the short RNA duplex, where familial mutations cluster. Analysis of the structure shows how aminoglycosides and related drugs bind to the RNA major groove, adding to our understanding of the principles of drug-RNA recognition.
| + | [[Category: Goedert M]] |
| - | | + | [[Category: Spillantini MG]] |
| - | ==About this Structure==
| + | [[Category: Varani G]] |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EI2 OCA]. | + | [[Category: Varani L]] |
| - | | + | |
| - | ==Reference==
| + | |
| - | Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics., Varani L, Spillantini MG, Goedert M, Varani G, Nucleic Acids Res. 2000 Feb 1;28(3):710-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10637322 10637322]
| + | |
| - | [[Category: Goedert, M]] | + | |
| - | [[Category: Spillantini, M G.]] | + | |
| - | [[Category: Varani, G.]] | + | |
| - | [[Category: Varani, L.]] | + | |
| - | [[Category: Aminoglycoside]]
| + | |
| - | [[Category: Frontotemporal dementia ftdp-17]] | + | |
| - | [[Category: Intronic mutation]] | + | |
| - | [[Category: Nmr]] | + | |
| - | [[Category: Rna]] | + | |
| - | [[Category: Rna major groove recognition]] | + | |
| - | [[Category: Tau]] | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:07:32 2008''
| + | |
