Cretu, Constantin

[["dc.bibliographiccitation.firstpage","265"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","273.e8"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Cretu, Constantin"],["dc.contributor.author","Agrawal, Anant A."],["dc.contributor.author","Cook, Andrew"],["dc.contributor.author","Will, Cindy L."],["dc.contributor.author","Fekkes, Peter"],["dc.contributor.author","Smith, Peter G."],["dc.contributor.author","Lührmann, Reinhard"],["dc.contributor.author","Larsen, Nicholas"],["dc.contributor.author","Buonamici, Silvia"],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2022-11-07T07:41:02Z"],["dc.date.available","2022-11-07T07:41:02Z"],["dc.date.issued","2018"],["dc.description.abstract","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."],["dc.identifier.doi","10.1016/j.molcel.2018.03.011"],["dc.identifier.pmid","29656923"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116954"],["dc.language.iso","en"],["dc.relation.eissn","1097-4164"],["dc.relation.issn","1097-2765"],["dc.relation.orgunit","Max-Planck-Institut für biophysikalische Chemie"],["dc.title","Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]