A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.
oleh: Matthew C Clifton, David M Dranow, Alison Leed, Ben Fulroth, James W Fairman, Jan Abendroth, Kateri A Atkins, Ellen Wallace, Dazhong Fan, Guoping Xu, Z J Ni, Doug Daniels, John Van Drie, Guo Wei, Alex B Burgin, Todd R Golub, Brian K Hubbard, Michael H Serrano-Wu
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2015-01-01 |
Deskripsi
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.