(A) Alignment of the BCL-2 core of BOK (green) and that of BAX, BCL-xL,
and BCL-w completed in PyMOL. The root-mean-square deviation is indicated for
the total number of atoms used in the alignment. Top: cartoon representations
indicate major deviations in alignments in the region connecting helices
α2–α4, which defines the atypical groove of BOK. Bottom:
cartoon-and-stick representations of BOK protruding through the surface
representation of the aligning partner. Clashes with incoming hydrophobic
ligands are predicted throughout the hydrophobic groove of BOK.
(B) The atypical hydrophobic groove of BOK is shown in the apo
configuration or interacting with the BID BH3 from the BID SAHB-BAK complex
(2m5b.pdb). Left: the electrostatic potential plotted on the surface of BOK.
Middle and right: the putative clashes of the BID BH3 ligand at the groove of
BOK. The chemical staple of the BID SAHB was excluded (right). The putative
hydrophobic pockets are designated as P0–P5.
(C) The alignment of BOK and the BAX-BIM SAHB complex showing a view of
the activation site of BAX engaged by BIM SAHB. The predicted structural clashes
and electrostatic incompatibilities of BIM SAHB and BOK at this site are
illustrated in the surface-cartoon representation, suggesting that their
interaction is disfavored. See also Figure S3.