Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.
Journal, issue, pages	Nat Commun, Vol. 12, Issue 1, Page 4491, Year 2021
Publish date	Jul 23, 2021
Authors	Constantin Cretu / Patricia Gee / Xiang Liu / Anant Agrawal / Tuong-Vi Nguyen / Arun K Ghosh / Andrew Cook / Melissa Jurica / Nicholas A Larsen / Vladimir Pena /
PubMed Abstract	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 ...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.
External links	Nat Commun / PubMed:34301950 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.4 - 3.1 Å
Structure data	12994 7onb EMDB-12994, PDB-7onb: Structure of the U2 5' module of the A3'-SSA complex Method: EM (single particle) / Resolution: 3.1 Å PDB-7b0i: Structure of a minimal SF3B core in complex with spliceostatin A (form II) Method: X-RAY DIFFRACTION / Resolution: 3.0 Å PDB-7b91: Structure of a minimal SF3B core in complex with pladienolide D (form I) Method: X-RAY DIFFRACTION / Resolution: 3.0 Å PDB-7b92: Structure of a minimal SF3B core in complex with sudemycin D6 (form II) Method: X-RAY DIFFRACTION / Resolution: 3.0 Å PDB-7b9c: Structure of a minimal SF3B core in complex with spliceostatin A (form I) Method: X-RAY DIFFRACTION / Resolution: 2.4 Å PDB-7omf: Structure of a minimal SF3B core in complex with sudemycin D6 (form I) Method: X-RAY DIFFRACTION / Resolution: 3.0 Å PDB-7opi: Structure of a minimal SF3B core in complex with the inactive modulator spliceostatin E (form I) Method: X-RAY DIFFRACTION / Resolution: 3.1 Å
Chemicals	ChemComp-SJT: spliceostatin A (form II) ChemComp-ZN: Unknown entry ChemComp-HOH: WATER / Water ChemComp-T2Z: [(2~{S},3~{S},4~{E},6~{S},7~{R},10~{R})-3,7-dimethyl-2-[(2~{E},4~{E},6~{R})-6-methyl-6-oxidanyl-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 ChemComp-T2W: [(~{Z},2~{S})-5-[[4-[(2~{E},4~{E})-3-methyl-5-[(2~{S},4~{R})-4,6,6-trimethyl-4-oxidanyl-oxan-2-yl]penta-2,4-dienyl]cyclohexyl]amino]-5-oxidanylidene-pent-3-en-2-yl] ~{N}-methylcarbamate ChemComp-SCN: THIOCYANATE ION / Thiocyanate ChemComp-07I: Spliceostatin E (form I)
Source	homo sapiens (human) unidentified adenovirus human (human) mus musculus (house mouse)
Keywords	SPLICING / SF3B / pre-mRNA splicing / splicing modulator / spliceostatin A / pladienolide D / sudemycin D6 / Splicing inhibitor / SF3B complex / Spliceosome / spliceostatin E