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Abstract
摘要 |
Protein design aims to identify new protein sequences of desirable structure and function. We developed a new method to engineer in silico proteins using evolutionary profiles of protein molecules. The method is used to design de novo XIAP (X-linked Inhibitor of Apoptosis) BIR3 domains, which suppress cell death by inhibiting the activity of Caspase-9. The in vivo activity of the XIAP proteins can be inhibited by the binding with the second mitochondria-derived activator of capases (Smac). The structure and function of the designed XIAP domains were biophysically characterized by circular dichroism, isothermal calorimetry, and NMR spectroscopy. Compared to the wild-type XIAP protein, the designed sequences show significantly enhanced folding stability and highly selective binding affinity between Smac peptide and Caspase-9 protein. |
