RT Journal Article
T1 The NMR structure of human obestatin in membrane-like environments: insights into the structure-bioactivity relationship of obestatin
A1 Otero Alén, Begoña
A1 Nieto, Lidia
A1 Gurriarán Rodríguez, Uxía
A1 Mosteiro, Carlos S.
A1 Álvarez Pérez, Juan Carlos
A1 Otero Alén, María
A1 Pérez Camiña, Jesús
A1 Gallego Gómez, María Rosalía
A1 García-Caballero Parada, Tomás
A1 Casanueva Freijo, Felipe
A1 Jiménez Barbero, Jesús
A1 Pazos Randulfe, Yolanda
AB The quest for therapeutic applications of obestatin involves, as a first step, the determination of its 3D solution structure and the relationship between this structure and the biological activity of obestatin. On this basis, we have employed a combination of circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, and modeling techniques to determine the solution structure of human obestatin (1). Other analogues, including human non-amidated obestatin (2) and the fragment peptides (6–23)-obestatin (3), (11–23)-obestatin (4), and (16–23)-obestatin (5) have also been scrutinized. These studies have been performed in a micellar environment to mimic the cell membrane (sodium dodecyl sulfate, SDS). Furthermore, structural-activity relationship studies have been performed by assessing the in vitro proliferative capabilities of these peptides in the human retinal pigmented epithelial cell line ARPE-19 (ERK1/2 and Akt phosphorylation, Ki67 expression, and cellular proliferation). Our findings emphasize the importance of both the primary structure (composition and size) and particular segments of the obestatin molecule that posses significant α-helical characteristics. Additionally, details of a species-specific role for obestatin have also been hypothesized by comparing human and mouse obestatins (1 and 6, respectively) at both the structural and bioactivity levels.
PB PLOS
YR 2012
FD 2012
LK http://hdl.handle.net/10347/21733
UL http://hdl.handle.net/10347/21733
LA eng
NO Alén BO, Nieto L, Gurriarán-Rodríguez U, Mosteiro CS, Álvarez-Pérez JC, Otero-Alén M, et al. (2012) The NMR Structure of Human Obestatin in Membrane-Like Environments: Insights into the Structure-Bioactivity Relationship of Obestatin. PLoS ONE 7(10): e45434. https://doi.org/10.1371/journal.pone.0045434
NO This work was supported by grants from Ministerio de Economía y Competitividad (SAF2010-20451, CTQ2009-08536), Xunta de Galicia (INCITE09PXIB 918374PR) and Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Spain; PS09/02202, PS09/02075). CIBER is an initiative of Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación, Spain). Instituto de Salud Carlos III and SERGAS fund the work of J.P. Camina, and Y. Pazos through a research-staff stabilization contract. Xunta de Galicia funds U. Gurriarán-Rodriguez through a research-staff contract Isabel Barreto
DS Minerva
RD 27 abr 2026