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PLoS One DOI:10.1371/journal.pone.0125010

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

Publication TypeJournal Article
Year of Publication2015
AuthorsClifton, 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
JournalPLoS One
Volume10
Issue4
Pagese0125010
Date Published2015
ISSN1932-6203
KeywordsApoproteins, 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
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.

URLhttp://dx.plos.org/10.1371/journal.pone.0125010
DOI10.1371/journal.pone.0125010
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25909780?dopt=Abstract

Alternate JournalPLoS ONE
PubMed ID25909780
PubMed Central IDPMC4409056