RT info:eu-repo/semantics/article
T1 Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members
A1 Hossein, Ali
A1 Espona Fiedler, Margarita
A1 Soto Cerrato, Vanessa
A1 Quesada Pato, Roberto
A1 Pérez Tomás, Ricardo
A1 Guallar, Victor
K1 Química orgánica
K1 Chemistry, Organic
AB Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that arecurrently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question.Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicatea large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstratethat prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulationswith the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecularinteractions. These results provide new data to understand the mechanism of action of these molecules, and assist in thedevelopment of more specific inhibitors of anti-apoptotic BCL-2 proteins.
PB Public Library of Science
SN 1932-6203
YR 2013
FD 2013-02
LK http://hdl.handle.net/10259/4240
UL http://hdl.handle.net/10259/4240
LA eng
NO Spanish government and the European Union (FIS-PI10/00338) and from the ERC-2009-Adg25027-PELE European project.
DS Repositorio Institucional de la Universidad de Burgos
RD 24-abr-2024