| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Stabilization of proteins (prevention of denaturation and aggregation) is important in drug development. Sulfobetaines are a class of protein stabilizer whose mechanisms remain elusive. To elucidate their stabilizing mechanisms, we analyzed their effects on protein dynamics. We found that NDSB-195 enhances the dynamics of β4-α2 loop of ubiquitin molecules and that NDSB-256 enhances the cis-trans isomerization of an Ala-Pro peptide bond. These effects may contribute the stabilizing activities of sulfobetaines by helping the denatured protein molecules escape from kinetic traps. In addition, by expressing proteins and peptides as fusion proteins, we succeeded in obtaining soluble complex of Gαi1 and its activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor. We also identified 3 residues in the peptide that are critical for the binding with Gαi1.
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