2003 Fiscal Year Final Research Report Summary
Studies of physiological function of D-aspartate in eukaryotic cells : from yeasts to mammals
| Project/Area Number |
14560064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用微生物学・応用生物化学
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| Research Institution | Nagoya University (2003)
Kyoto University (2002) |
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Principal Investigator |
MORIYAMA Ryuichi Nagoya University, Graduate School of Bioagricultural Science, Associate Professor, 大学院・生命農学研究科, 教授 (70182821)
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| Co-Investigator(Kenkyū-buntansha) |
森山 龍一 名古屋大学, 大学院・生命農学研究科, 助教授 (60191061)
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| Project Period (FY) |
2002 – 2003
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| Keywords | D-amino acid / racemase / eukaryote / yeast / D-amino acid N-acetyltransferase |
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| Research Abstract |
We studied functions of the eukaryotic genes encoding putative D-amino acid-related enzymes. We found that dao 1^+, alr 1^+, alr 2^+, and srf1^+ of Schizosaccharomyces pombe encode D-amino acid oxidase, alanine racemase, arginine racemase, and serine racemase, respectively. Saccharomyces cerevisiae cells were reported to contain D-amino acid N-acetyltransferase, however its gene has been unknown. We found that the enzyme is encoded by HPA3, the gene of a putative histone/protein acetyltransferase belonging to Gcn5-related N-acetyltransferase superfamily. The gene product, Hpa3p, acts on a wide range of D-amino acids but none of L-amino acids. Hpa3p shares 49% sequence identity and 81% sequence similarity with Hpa2p, a yeast histone acetyltransferase. However, Hpa3p shows little histone acetyltransferase activity, and Hpa2p has no detectable acetyltransferase activities towards D-or L-amino acids tested except for the trace activity towards D-and L-lysine. Kinetic analyses suggest that Hpa3p catalyzes the acetylation of D-amino acids with an ordered bi-bi mechanism, in which acetyl-CoA is the first substrate to be bound and CoA is the last product to leave. Hpa3p was revealed to be involved in lowering the inhibitoru effect of various D-amino acids. We also studied the function of the mouse PROSC protein, a homolog of S. cerevisiae Yb1036cp, which has no sequencial homology but has similar three-dimensional structure to that of the N-terminal domain of bacterial alanine racemase.
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