A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.

PLoS One
Authors
Keywords
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.

Year of Publication
2015
Journal
PLoS One
Volume
10
Issue
4
Pages
e0125010
Date Published
2015
ISSN
1932-6203
URL
DOI
10.1371/journal.pone.0125010
PubMed ID
25909780
PubMed Central ID
PMC4409056
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