The proteins of pancreatic ribonuclease (Rnase) superfamily are enzymes which constitute optimal models for the study of processes such as catalysisi, enzyme-substrate binding, protein stability and folding. Given the involvement of some members of this class of proteins on several cell events and its use as therapeutic drugs new possibilities are now open to study. In this project four goals have been defined: 1. Characterization of the enzyme-substrate binding, catalysis and molecular basis of Rnases stability, through the study of ribonuclease A (Rnase A), eosinophil cationic proteic (ECP) human pancreatic Rnase (HP-Rnase) and Rnase8. Rnase a will be chosen model because of the amount data already available on this subject and the cleavage pattern of polymeric substrate will be analysed. 2. Study of the molecular basis involved in the bniological functions of the eosinophil cationic protein (ECP) and other Rnases. This goal will contribuite to the molecular and cellular knowledge of ECP and includes different approaches as structural studies of ECP and other Rnases, the molecular basis of cytotoxicity the ECP expression pattern in specific cell lines and the characterization of the cat eosinophil proteins, chosen as an animal model. 32. Mapping the hydrophobic core residues opf pancreatic Rnases: contributions of some critical amino acids tio the general stability and folging/yunfolding pathwqy under the effect of pressure. Information about the effect of pressure in the proten structure and the basis of protein stability will be used to the design of proteins with specific biological functions.4. Design production and characterization of new cytotoxic HP-Rnase and oncoase varainta in order to better understand the molecular basis of the cytotoxic mechanisms of Rnases. Based on structural analysis of HP-Rnase and onconase, this study will contribute through different approaches to determine key factors related to the production of Rnases as therapeuti
|Effective start/end date||1/12/03 → 30/11/06|
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