|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Clifton, MC, Dranow, DM, Leed, A, Fulroth, B, Fairman, JW, Abendroth, J, Atkins, KA, Wallace, E, Fan, D, Xu, G, Ni, ZJ, Daniels, D, Van Drie, J, Wei, G, Burgin, AB, Golub, TR, Hubbard, BK, Serrano-Wu, MH|
|Keywords||Apoproteins, Crystallization, Crystallography, X-Ray, Drug Design, Humans, Ligands, Maltose-Binding Proteins, Models, Molecular, Myeloid Cell Leukemia Sequence 1 Protein, Peptide Fragments, Protein Binding, Protein Conformation, Recombinant Fusion Proteins|
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.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC4409056|