English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
 Local TagsRelease HistoryDetailsSummary
  Structural basis of splicing modulation by antitumor macrolide compounds.

Cretu, C., Agrawal, A. A., Cook, A., Will, C. L., Fekkes, P., Smith, P. G., et al. (2018). Structural basis of splicing modulation by antitumor macrolide compounds. Molecular Cell, 70(2), 265-273. doi:10.1016/j.molcel.2018.03.011.

Item is

 

show all hide all

Basic

show hide
Item Permalink: https://hdl.handle.net/21.11116/0000-0001-2921-C Version Permalink: https://hdl.handle.net/21.11116/0000-0003-479C-E
Genre: Journal Article

Files

show Files
hide Files
:
2578317.pdf (Publisher version), 4MB
 
File Permalink:
-
Name:
2578317.pdf
Description:
-
OA-Status:
Visibility:
Restricted ( Max Planck Society (every institute); )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2578317_Suppl_1.pdf (Supplementary material), 2MB
View   Save
File Permalink:
https://hdl.handle.net/21.11116/0000-0001-31D8-4
Name:
2578317_Suppl_1.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
View
Copyright Date:
-
Copyright Info:
-
License:
-
:
2578317_Suppl_2.pdf (Supplementary material), 5MB
View   Save
File Permalink:
https://hdl.handle.net/21.11116/0000-0001-31D9-3
Name:
2578317_Suppl_2.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
View
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Cretu, C.1, Author           
Agrawal, A. A., Author
Cook, A., Author
Will, C. L.2, Author           
Fekkes, P., Author
Smith, P. G.,, Author
Lührmann, R.2, Author           
Larsen, N., Author
Buonamici, S., Author
Pena, V.1, Author           
Affiliations:
1Research Group of Macromolecular Crystallography, MPI for Biophysical Chemistry, Max Planck Society, ou_2035293              
2Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              

Content

show
hide
Free keywords: A complex; SF3b; alternative splicing; antitumor drug; branch site; pre-mRNA splicing; spliceosome; splicing modulator
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2018-03-242018-04-19
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2018.03.011
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Molecular Cell
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 70 (2) Sequence Number: - Start / End Page: 265 - 273 Identifier: -