4 resultados para Alfieri, Vittorio, 1749-1803.

em Archivo Digital para la Docencia y la Investigación - Repositorio Institucional de la Universidad del País Vasco


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Eguíluz, Federico; Merino, Raquel; Olsen, Vickie; Pajares, Eterio; Santamaría, José Miguel (eds.)

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[ES]Si hasta mediados del siglo XVIII la jurisdicción sobre los bosques guipuzcoanos fue acumulativa y a prevención entre las instituciones provinciales, los alcaldes, el Corregidor y las instituciones de Marina, la Real Cédula de 28 de junio de 1749 inauguró un nuevo período en el que la Provincia la detentó de forma privativa y excluyente, lo que provocó un choque frontal con el Corregidor, quien se resistía a dejar de ejercer sus prerrogativas.

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460 pgs.

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Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins.