6en4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==SF3b core in complex with a splicing modulator== | |
| + | <StructureSection load='6en4' size='340' side='right'caption='[[6en4]], [[Resolution|resolution]] 3.08Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6en4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EN4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EN4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGZ:[(2~{S},3~{S},4~{E},6~{S},7~{R},10~{R})-3,7-dimethyl-2-[(2~{E},4~{E},6~{S})-6-methyl-7-[(2~{R},3~{R})-3-[(2~{R},3~{S})-3-oxidanylpentan-2-yl]oxiran-2-yl]hepta-2,4-dien-2-yl]-7,10-bis(oxidanyl)-12-oxidanylidene-1-oxacyclododec-4-en-6-yl]+ethanoate'>BGZ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ife|5ife]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6en4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6en4 OCA], [http://pdbe.org/6en4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6en4 RCSB], [http://www.ebi.ac.uk/pdbsum/6en4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6en4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PHF5A_HUMAN PHF5A_HUMAN]] Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha. Also involved in pre-mRNA splicing.<ref>PMID:12234937</ref> [[http://www.uniprot.org/uniprot/SF3B3_HUMAN SF3B3_HUMAN]] Subunit of the splicing factor SF3B required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron. [[http://www.uniprot.org/uniprot/SF3B1_HUMAN SF3B1_HUMAN]] Subunit of the splicing factor SF3B required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SF3B is a multi-protein complex essential for branch site (BS) recognition and selection during pre-mRNA splicing. Several splicing modulators with antitumor activity bind SF3B and thereby modulate splicing. Here we report the crystal structure of a human SF3B core in complex with pladienolide B (PB), a macrocyclic splicing modulator and potent inhibitor of tumor cell proliferation. PB stalls SF3B in an open conformation by acting like a wedge within a hinge, modulating SF3B's transition to the closed conformation needed to form the BS adenosine-binding pocket and stably accommodate the BS/U2 duplex. This work explains the structural basis for the splicing modulation activity of PB and related compounds, and reveals key interactions between SF3B and a common pharmacophore, providing a framework for future structure-based drug design. | ||
| - | + | Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds.,Cretu C, Agrawal AA, Cook A, Will CL, Fekkes P, Smith PG, Luhrmann R, Larsen N, Buonamici S, Pena V Mol Cell. 2018 Apr 19;70(2):265-273.e8. doi: 10.1016/j.molcel.2018.03.011. Epub, 2018 Apr 12. PMID:29656923<ref>PMID:29656923</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6en4" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cretu, C]] | ||
| + | [[Category: Pena, V]] | ||
| + | [[Category: Protein complex]] | ||
| + | [[Category: Splicing]] | ||
| + | [[Category: Splicing modulator]] | ||
Current revision
SF3b core in complex with a splicing modulator
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