| Literature DB >> 29149594 |
Jason M Brouwer1, Ping Lan1, Angus D Cowan1, Jonathan P Bernardini1, Richard W Birkinshaw1, Mark F van Delft1, Brad E Sleebs1, Adeline Y Robin1, Ahmad Wardak2, Iris K Tan2, Boris Reljic1, Erinna F Lee3, W Douglas Fairlie3, Melissa J Call1, Brian J Smith4, Grant Dewson1, Guillaume Lessene5, Peter M Colman1, Peter E Czabotar6.
Abstract
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation.Entities:
Keywords: Bak; Bcl-2 family; Bim; apoptosis; inhibitor; non-natural amino acid
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Year: 2017 PMID： 29149594 DOI： 10.1016/j.molcel.2017.11.001
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970