Caracterització de determinants estructurals de propietats especials de la ribonucleasa pancreàtica humana

• Autores: Pere Tubert Juhé
• Directores de la Tesis: Antoni Benito Mundet (dir. tes.), Maria Vilanova Brugués (dir. tes.)
• Lectura: En la Universitat de Girona ( España ) en 2012
• Idioma: catalán
• Tribunal Calificador de la Tesis: Claudi Cuchillo Foix (presid.), Mercè Figueras i Vall-llosera (secret.), Marta Bruix Bayes (voc.), Joan Torrent i Mas (voc.), Francesc Canals Suris (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Ribonucleases are promising candidates for use in anticancer therapy. There are different ways to endow an RNase with antitumor properties. Targeting the enzyme to the cell nucleus is a potential approach. PE5 is a variant of HP-RNase that it’s cytotoxic because it contains a nuclear localization signal. It has been shown that this sequence allows its interaction with ?-importin. An alternative strategy to endow an RNase with cytotoxic activity is its dimerization. An HP-RNase variant, PM8, which forms a dimer through domain swapping, was produced in solution. This variant dimerized through a two-steps mechanism of domain swapping. To prove his model several variants of PM8 were produced in which the side chains of residues involved were removed. The variation of flexibility of the resulting hinge peptides and the effect of these changes on the ability of the variants to swap domains and to dimerize was determined