Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/43816
Title: Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members.
Author: Hosseini, A.
Espona Fiedler, Margarita
Soto Cerrato, Vanessa
Quesada, R.
Pérez Tomás, Ricardo E.
Guallar, V.
Keywords: Genètica molecular
Medicaments antineoplàstics
Melanoma
Molecular genetics
Antineoplastic agents
Melanoma
Issue Date: 27-Feb-2013
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a: http://dx.doi.org/0.1371/journal.pone.0057562
It is part of: PLoS One, 2013, vol. 8, num. 2, p. e57562
Related resource: http://dx.doi.org/10.1371/journal.pone.0057562
URI: http://hdl.handle.net/2445/43816
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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