2010 Fiscal Year Final Research Report
Structure analyses of key enzymes from trypanosoma and malaria for the development of new drugs
| Project/Area Number |
19370043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
YOSHIMOTO Tadashi Nagasaki University, 理工学部, 教授 (60088870)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Kiyoshi 長崎大学, 医歯薬学総合研究科, 准教授 (50201926)
NAKAJIMA Yoshitaka 長崎大学, 医歯薬学総合研究科, 助教 (80372770)
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| Project Period (FY) |
2007 – 2010
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| Keywords | マラリア / トリパノソーマ / オリゴペプチダーゼB / 阻害剤 / 医薬品 |
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| Research Abstract |
Since there is no effective medicine for infectious disease caused by Trypanosoma and malaria, many peoples live in tropical were killed. In order to develop new drugs for these, we focused to metabolic enzymes in Trypanosoma and malalia as target, and studied specific inhibitors.
(1) Methionine aminopeptidase from P. falciparum ; We develop new assay method of methionine aminopeptidase using prolyl aminopeptidase. We cloned the enzyme gene and expressed in E. coli. Using the new assay method, specific inhibitor have been screened. A family of structurally related inhibitors containing a 2-(2pyridinyl)- pyrimidine was identified in compound library. Inhibitors were also found in microbial products and plant extract.
(2) Oligopeptidase B from trypanosomiasis : The enzyme plays a key role in the pathogenesis of trypanosomiasis. We found protamine act unique and potent inhibitor for oligopeptidase B from trypanosoma. In order to clarify the mechanism of inhibition, we crystallized the enzyme and studied X-ray crystallography. The crystallographic parameters were a=b=123.9, C=248.0 A gamma=120 degree and p hexagonal.
(3) Specific inhibitors for aminopeptidase N and prolyl oligopeptidase from them were also studied.
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[Journal Article] Substitution of Glu122 by glutamine revealed the function of the second water molecule as a proton donor in the binuclear metal enzyme, creatininase2010
Author(s)
Yamashita K., Nakajima Y., Matsushita H., Nishiya Y., Yamazawa R., Wu Y., Matsubara F., Oyama H., Ito K., Yoshimoto T.
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Journal Title
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[Presentation]2009
Organizer
プロリン特異性ペプチダーゼ生化学会シンポジウム
Place of Presentation
神戸
Year and Date
2009-10-22
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