2024-03-28T19:47:00Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/42402021-11-10T09:38:19Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members
Hossein, Ali
Espona Fiedler, Margarita
Soto Cerrato, Vanessa
Quesada Pato, Roberto
Pérez Tomás, Ricardo
Guallar, Victor
Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are
currently 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-2
protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate
a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate
that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations
with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular
interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the
development of more specific inhibitors of anti-apoptotic BCL-2 proteins.
2016-09-22T09:02:35Z
2016-09-22T09:02:35Z
2016-09-22T09:02:35Z
2013-02
info:eu-repo/semantics/article
1932-6203
http://hdl.handle.net/10259/4240
10.1371/journal.pone.0057562
eng
PLoS ONE. 2013, V. 8, n. 2, e57562
http://dx.doi.org/10.1371/journal.pone.0057562
info:eu-repo/grantAgreement/UE/FIS-PI10/00338
info:eu-repo/grantAgreement/EC/FP7/25027
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Attribution 4.0 International
Public Library of Science