| Project/Area Number |
07280103
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
YUTANI Katsuhide Inst. Protein Res., Osaka Univ., Assoc. Prof., タンパク質研究所, 助教授 (90089889)
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| Co-Investigator(Kenkyū-buntansha) |
KATAOKA Mikio Nara Inst. Sci. Tech., Professor, 物質創成科学, 教授 (30150254)
KUSHIDA Takashi Nara Inst. Sci. Tech., Professor, 物質創成科学, 教授 (00013516)
YAMAGATA Yuriko Grad.Schl. Pharm. Sci., Osaka Univ., Assoc. Prof., 大学院・薬学研究科, 助教授 (40183678)
KIDERA Akinori Grad. Schol. Sci., Kyoto Univ., Assoc. Prof., 大学院・理学研究科, 助教授 (00186280)
KIDOKORO Shunichi Sagami Chem. Res. Inst., Senior Res. Scientist, 副主任研究員
熊谷 泉 東北大学, 大学院・工学研究科, 教授 (10161689)
伊倉 貞吉 東京大学, 大学院・理学系研究科, 助手 (50251393)
北尾 彰朗 京都大学, 大学院・理学研究科, 助手 (30252422)
後藤 祐児 大阪大学, 理学部, 助教授 (40153770)
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| Project Period (FY) |
1995 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥244,200,000 (Direct Cost: ¥244,200,000)
Fiscal Year 1998: ¥46,600,000 (Direct Cost: ¥46,600,000)
Fiscal Year 1997: ¥62,200,000 (Direct Cost: ¥62,200,000)
Fiscal Year 1996: ¥67,000,000 (Direct Cost: ¥67,000,000)
Fiscal Year 1995: ¥68,400,000 (Direct Cost: ¥68,400,000)
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| Keywords | Protein Conformation / Stability of Protein / Dynamics of Protein / Protein Folding / Lysozyme / Calorimetry / X-ray crystal analyses / タンパク質 / 立体構造 / 安定性 / 折れたたみ機構 / 熱測定 / ダイナミックス |
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| Research Abstract |
In order to analyze "principles of protein architecture", that is, the principle of how protein three-dimensional structures are coded for in their amino acid sequence, we have studied physico-chemical aspects of protein conformation. To do it there are two major groups : (1) a thorough study of a model protein, human lysozyme and (2) a study of important projects on protein stability, protein dynamics, and protein folding. As to the first project (Yutani, Yamagata, and Kitao), more than 100 mutant human lysozymes with systematic and comprehensive substitutions are constructed. Changes in stabilities and structures due to mutations were examined by calorimetry and X-ray analysis, respectively. On the basis of the obtained stability-structure data-base, the relationship between changes in stability and structure due to mutations was examined and each parameter of stabilization factors could be successfully estimated after due consideration on such as secondary structure propensity, introduction of water, formation and removal of hydrogen bond, differences in accessible surface area of polar and non-polar atoms due to denaturation. These results indicate that (1) non-polar atoms play an important role in protein stability but polar atoms do not, (2) if a hydrogen bond in which the length is 3 A is removed due to substitution, the mutant protein should be destabilized by 8.6 kJ/mol, (3) when one water molecule is newly introduced in the interior of a protein, it is destabilized by 7.2 kJ/mol due to entropic effect. As to the second project, Kidokoro and Yutani studied stability of proteins from thermophile. Kushide developed time-resolved hole-burning spectroscopy by himself and examined conformational fluctuations and dynamics of Zn-substituted myoglobin. Kidera, Kataoka, Kuwajima, and Goto studied important problems of dynamics, protein folding, and non-native structures of a protein. Kumagai and Kidokoro also studied important problems of protein function.
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