1993 Fiscal Year Final Research Report Summary
Studies on catalytic mechanism of prolyl endopeptidase by genetic method and biological significance of it in the brain
| Project/Area Number |
03454493
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
YOSHIMOTO Tadashi NAGASAKI UNIVERSITY, School of Pharm. Associate Professor, 薬学部, 助教授 (60088870)
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| Project Period (FY) |
1991 – 1993
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| Keywords | prolyl endopeptidase / peptidase / protease / Alzheimer's disease / protease II / プロテアーゼ |
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| Research Abstract |
The prolyl endopeptidase [EC 3.4.21.26] genes of Flavobacterium meningosepticum, A.hydrophila, and bovine brain, and protease II gene from E.coli were cloned. A high conservation of primary structure is observed among these four enzumes. Surprisingly, C-terminal regions of prolyl endopeptidase show significant homology to following proteins : pig and rat acyl-amino acid releasing enzymes, human protein 3P21, rat and human dipeptidyl aminopeptidases IV, yeast dipeptidyl aminopeptidase B, and X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. The amino acid residues of the catalytic triad are well conserved. These enzymes have also common characteristics on oligopeptides. Thus, presence of prolyl oligpeptidase family was proposed as a new family of serine endopeptidases.
Amyloid b/A4 peptide is one of the integral components that are typically manifested in senile plaques and cerebrovascular amyloids in the patients with Alzheimer's disease. I ascertained for the first time the distribution of prolyl endopeptidase in senescence accelerated mouse (SAM) by the immunostaining method. I also found that prolyl endopeptidase and amyloid b/A4 peptide distributed with close relationships in the hippocampus. These result suggest that prolyl endopeptidase is involved in the processes to form amyloid deposition in the brain of SAM.
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[Publications] Yoshimoto, T., Yamamoto, N., Ogawa, H., Furukawa, S., and Tsuru, D: "Specific inhibition of dipeptidyl aminopeptidase IV by a new synthetic inhibitor, L-thioprolylthiazolidine." Agric.Biol.Chem.55. 1135-1136 (1991)
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[Publications] Yoshimoto, Higashi, H., Kanatani, A., Xu, S-L., Nagai, H., Oyama, H., Kurazono, K., and Tsuru, D: "Cloning and sequencing of the 7-a-hydroxysteroid dehydrogenase gene from Escherichia coli HB101 and characterization of the expressed enzyme" J.Bacteriol.173. 2173-2179 (1991)
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[Publications] Kanatani, A., Masuda, T., Shimoda, T., Xu, S.L., Yoshimoto, T., and Tsuru, D: "Protease II from Escherichia coli : Sequencing and expression of the enzyme gene and characterization of the expressed enzyme" J.Biochem.110. 315-320 (1991)
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[Publications] Yoshimoto, T., Knatani, A., Shimoda, T., Inaoka, T., Kokubo, T., and Tsuru, D: "Prolyl endopeptidse from Flavobacterium meningosepticum : Cloning and sequencing of the enzyme gene" J.Biochem.110. 873-878 (1991)
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[Publications] Yoshimoto, T., Shimoda, T., Kitazono, A., Kabashima, T., Ito, K., and Tsuru, D: "Pyroglutamyl peptidase gene from Bacillus amyloliquefaciens : cloning, Sequencing, expression, and crystallization of the expressed enzyme" J.Biochem.113. 67-73 (1993)
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[Publications] Kanatani, A., Yoshimoto, T., Kitazono, A., Kokubo, T., and Tsuru, D: "Prolyl endopeptidase from Aeromonas hydrophyla : cloning, sequencing, and expression of the enzyme gene, and characterization of the expressed enzyme" J.Biochem.113. 790-796 (1993)
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「研究成果報告書概要(欧文)」より
