http://hdl.handle.net/10362/3418 2013-05-18T20:29:22Z http://hdl.handle.net/10362/5151 Title: Metal ions and protein folding: conformational and functional interplay Authors: Botelho, Hugo M. Abstract: Metal ions are cofactors in about 30% of all proteins, where they fulfill catalytical and structural roles. Due to their unique chemistry and coordination properties they effectively expand the intrinsic polypeptide properties (by participating in catalysis or electron transfer reactions), stabilize protein conformations (like in zinc fingers) and mediate signal transduction (by promoting functionally relevant protein conformational changes). However, metal ions can also exert have deleterious effects in living systems by incorporating in non-native binding sites, promoting aberrant protein aggregation or mediating redox cycling with generation of reactive oxygen and nitrogen species. For this reason, the characterization of the roles of metal ions as modulators of protein conformation and stability provides fundamental knowledge on protein folding properties and is instrumental in establishing the molecular basis of disease. In this thesis we have analyzed protein folding processes using model protein systems incorporating covalently bound metal cofactors – iron-sulfur (FeS) proteins – or where metal ion binding is reversible and associated conformational readjustments – the S100 proteins.(...) Description: Dissertation presented to obtain a PhD degree in Biochemistry at Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa 2010-11-01T00:00:00Z http://hdl.handle.net/10362/5150 Title: Defective protein folding and function in metabolic disorders: studies on the mitochondrial flavoenzyme ETF Authors: Henriques, Bárbara J. Abstract: The work presented in this dissertation concerns the study of the electron transfer flavoprotein (ETF), a protein involved in mitochondrial β-oxidation whose deficiency is associated to multiple acyl-CoA dehydrogenase deficiency (MADD). The thesis will focus on establishing the functional, cellular and molecular consequences of the genetic variability in ETF, and in particular it aims to clarify the basis for the effect of heat stress on disease progression. Moreover, the beneficial effects of vitamin B2 supplementation will be addressed.(...) Description: Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa 2010-10-01T00:00:00Z http://hdl.handle.net/10362/3567 Title: Protein folding, metal ions and conformational states: the case of a di-cluster ferredoxin Authors: Leal, Sónia S. Abstract: Metal ions are present in over thirty percent of known proteins. Apart from a well established function in catalysis and electron transfer, metals and metal centres are also important structural elements which may as well play a key role in modulating protein folding and stability. In this respect, cofactors can act not only as local structural stabilizing elements in the native state, contributing to the maintenance of a given specific structural fold, but may also function as potential nucleation points during the protein folding process... Description: Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa 2010-01-01T00:00:00Z