5VWZ

Bak in complex with Bim-h3Pc

Summary for 5VWZ

• Entry DOI: 10.2210/pdb5vwz/pdb
• Descriptor: Bcl-2 homologous antagonist/killer, Bcl-2-like protein 11, 2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL, ... (5 entities in total)
• Functional Keywords: apoptosis, bcl-2 family, inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 45262.74

Authors

Brouwer, J.M.,Colman, P.M.,Czabotar, P.E. (deposition date: 2017-05-23, release date: 2017-11-15, Last modification date: 2024-10-23)

Primary citation

Brouwer, J.M.,Lan, P.,Cowan, A.D.,Bernardini, J.P.,Birkinshaw, R.W.,van Delft, M.F.,Sleebs, B.E.,Robin, A.Y.,Wardak, A.,Tan, I.K.,Reljic, B.,Lee, E.F.,Fairlie, W.D.,Call, M.J.,Smith, B.J.,Dewson, G.,Lessene, G.,Colman, P.M.,Czabotar, P.E.
Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design.
Mol. Cell, 68:659-672.e9, 2017

PubMed 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.

PubMed: 29149594
DOI: 10.1016/j.molcel.2017.11.001

Experimental method

X-RAY DIFFRACTION (1.622 Å)