Fig. 5: Binding of Eltrombopag to the BAK α4/α6/α7 groove induces a BAK conformational change.
From: Eltrombopag directly activates BAK and induces apoptosis
a–c Overall view of Eltro binding to BAK at the α4/α6/α7 groove as depicted in a cartoon model (a) and a cartoon plus surface model (b) without Eltro (c). d Closeup view of Eltro binding to the BAK α4/α6/α7 groove showing involvement of BAK R156 and H164 in Eltro binding. e, f Cartoon models showing molecular interactions of Etro with R156 (e), F157, and H164 f. g, h Surface models showing Eltro induces a hydrophobic pocket on BAK α4/α6/α7 groove. Models show BAK with Eltro (g) and without Eltro (h). i–k Conformational change of two groups of BAK residues (Group #1: Q153 and R156 shown in red; Group #2: Y108, H164, and H165 shown in orange) induced by Eltro to expose the α4/α6/α7 groove. i before adding Eltro; j after adding Eltro; k, with Eltro. l Comparison of RMSF per BAK residue when BAK structure (PDB: 2IMS) was used to perform molecular dynamics simulations with or without Eltro.
