1) Metallothioneins: structure/function relationship: evolution and biotechnological applications.

Metallothioneins (MT) are small, cysteine-rich proteins, with high metal coordination capacity and increased reactivity with respect to free radicals. MT peptidesconstitute an extremely heterogeneous protein family, with no phylogenetic patterns defined or any physiological functions assigned. Primary and tertiary MT structure analysis, as well as that of MT structure/function relationships, will shed light onto the interaction between protein molecules and metal ions. Additionally, it will provide the bases to design and assay biotechnological schemes aimed both at bioremediation and biomedicine. MT characterization is performed at different levels through recombinant synthesis in the bacterial expression systems of MT forms belonging to several taxons. Biotechnological exploitation of MT features focuses on heterologous MT expression systems for two main purposes: first, heavy-metal removal from soil or water environments, and second, the design of new therapeutic agents for several physiological disorders in which MT appears to be involved.

Study at genomic and proteomic level of the organism global response towards metals, which includes different conditions, i.e. depletion and excess, regarding metal availability and intake. “Metals in Biology” research is gradually being focused on the integrative knowledge of all the elements (basically proteins) that are involved in this response, their interactions and their regulation. In our group, we study how S.cerevisiae acts in response to zinc overload, and the relationship between this response and other metabolic mechanisms and pathways.

[see Research Project 1 for the personnel involved]

This research is developed as a collaboration with the group of the Genetics Department working on the analysis of the genetic basis of Human Lysosomal and Cardio-Vascular Disorders. Our goal is the analysis of the effect of the amino acid substitutions described in different patients in the three-dimensional structure of the enzymes responsible of these diseases, and therefore the description of the enzymatic function alterations that may be the ultimate cause of the physiological disorders associated with the mutations. The 3D structure of some of these proteins has been already solved, but it is necessary to work on homology- or threading-models for the rest of them. Furthermore, in silico molecular interaction models for substrate or cofactor molecules are being built following molecular docking strategies. Current diseases and proteins studied are, respectively: the Gaucher disease (acid-ß-glucosidase or glucocerebrosidase), the GM1 Gangliosidosis and the Morquio B disease (ß-galactosidase) and the Marotaux-Lamy disease (aril-sulfatase). In relation to homocystinuria, cystathionine-ß-sintase is being analyzed.

Staff
Dr. Susana Balcells
Dr. Bru Cormand
Dr. Daniel Grinberg
Dr. Lluïsa Vilageliu


Collaborators
Dr. Alfonso Valencia (CNIO, Madrid)