Document Type
Article
Publication Date
4-24-2015
Publication Source
PLOS One
Abstract
Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.
ISBN/ISSN
1932-6203
Document Version
Published Version
Copyright
Copyright © 2015 Clifton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher
PLOS
Volume
10
Peer Reviewed
yes
Issue
4
Sponsoring Agency
Carlos Slim Health Institute and the Robertson Foundation
eCommons Citation
Clifton, Matthew C.; Dranow, David M.; Leed, Alison; Fulroth, Ben; Fairman, James W.; Abendroth, Jan; Atkins, Kateri A.; Wallace, Ellen; Fan, Dazhong; Xu, Guoping; Ni, Z. J.; Daniels, Douglas S.; Van Drie, John; Wei, Guo; Burgin, Alex B.; Golub, Todd R.; Hubbard, Brian K.; and Serrano-Wu, Michael H., "A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1" (2015). Chemistry Faculty Publications. 97.
https://ecommons.udayton.edu/chm_fac_pub/97
