7b9c
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| - | ==== | + | ==Structure of a minimal SF3B core in complex with spliceostatin A (form I)== |
| - | <StructureSection load='7b9c' size='340' side='right'caption='[[7b9c]]' scene=''> | + | <StructureSection load='7b9c' size='340' side='right'caption='[[7b9c]], [[Resolution|resolution]] 2.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7b9c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B9C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B9C FirstGlance]. <br> |
| - | </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=7b9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b9c OCA], [https://pdbe.org/7b9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b9c RCSB], [https://www.ebi.ac.uk/pdbsum/7b9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b9c ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=SJT:[(~{Z},2~{S})-5-[[(2~{R},3~{R},5~{S},6~{S})-6-[(2~{E},4~{E})-5-[(2~{R},3~{R},4~{S},6~{S})-6-methoxy-4,6-dimethyl-3,4-bis(oxidanyl)oxan-2-yl]-3-methyl-penta-2,4-dienyl]-2,5-dimethyl-oxan-3-yl]amino]-5-oxidanylidene-pent-3-en-2-yl]+ethanoate'>SJT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7b9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b9c OCA], [https://pdbe.org/7b9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b9c RCSB], [https://www.ebi.ac.uk/pdbsum/7b9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b9c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept. | ||
| + | |||
| + | Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.,Cretu C, Gee P, Liu X, Agrawal A, Nguyen TV, Ghosh AK, Cook A, Jurica M, Larsen NA, Pena V Nat Commun. 2021 Jul 23;12(1):4491. doi: 10.1038/s41467-021-24741-1. PMID:34301950<ref>PMID:34301950</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7b9c" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Cretu C]] | ||
| + | [[Category: Pena V]] | ||
Current revision
Structure of a minimal SF3B core in complex with spliceostatin A (form I)
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