Fig. 4: Allosteric mechanism of 643943 disrupting XIAP:CASP7. | Cell Death & Disease

Fig. 4: Allosteric mechanism of 643943 disrupting XIAP:CASP7.

From: Blocking XIAP:CASP7-p19 selectively induces apoptosis of CASP3/DR malignancies by a novel reversible small molecule

Fig. 4

A Sub-G0 cell populations of MCF-7, MCF-7 transfected with vector only, and MCF-7 variant cells stably expressing CASP7 with D93L mutation (MCF7_D93L) after treatment with I-Lys (1 μM), STS (1 μM), and 643943 (20 μM) for 24 h. B The binding mode of 119, an analog of 643943 without the D93 interacting OH group. C Sub-G0 cell populations of MCF-7 cells treated with 643943 and 119 measured by flow cytometry. The results showed no 119 induced-sub-G0 accumulation in MCF-7 cells, suggesting D93 is a key interacting residue for XIAP:CASP7 PPI. D Hydrogen bound interaction networks among significant residues of XIAP:CASP7 interface and four core residues (D93, A96, Q243, and C246) of the allosteric site are shown. D93 is indirectly (via S239) linked to three interacting residues in the linker preceding BIR2, especially D148.

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