| Project/Area Number |
24550189
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
MATSUO Takashi 奈良先端科学技術大学院大学, 物質創成科学研究科, 准教授 (50432521)
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| Co-Investigator(Renkei-kenkyūsha) |
HIROTA Shun 奈良先端科学技術大学院大学, 物質創成科学研究科, 教授 (90283457)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | カスパーゼ / 有機小分子 / アポトーシス / 作用機構 / PAC-1 / 活性化 / 速度論 |
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| Outline of Final Research Achievements |
Caspase-3, a protease at the downstream of a apoptosis cascade, is produced from a zymogen protein (procaspase-3) with the help of other activator on cell stimuli. The activation process is inhibited in several kinds of cancerous cell because of much amounts of metal ions. This work focuses on the action mechanism of PAC-1, a compoound that recovers the activation process of procaspase-3 in cencerous cells, on the activities of (pro)caspase-3 from the viewpoint of enzymology. The kinetic studies of caspase-3 indicated that PAC-1 enhances the activity of mature caspase-3 as well as the recovery of activation process from the zymogen to mature form in the absence of metal ions. The effect of the compound on a mutant procaspase-3, a variant that has a weak caspase-3 activity, was found to be poor. In conclusion, PAC-1 has a structural perturbation mechanismis for affecting the (pro)caspase-3 activities as well as the metal ion-chelation removal pathway.
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