| 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)
三原 久明 京都大学, 化学研究所, 助手 (30324693)
栗原 達夫 京都大学, 化学研究所, 助手 (70243087)
江崎 信芳 京都大学, 化学研究所, 教授 (50135597)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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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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