D-Amino acids in eucaryotic cells: physiological function and its molecular mechanism.

真核细胞中的 D-氨基酸：生理功能及其分子机制。

• 批准号: 16380069
• 负责人: YOSHIMURA Tohru
• 金额: $ 9.98万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16380069/
• 关键词: D-amino acid; racemase; D-amino acid oxidase; D-serine dehydratase; yeast; cellular slime mold; silkworm; D-セリン; セリンラセマーゼ; D-アラニン; アラニンラセマーゼ

D-Amino acids had been believed to occurr only in lower organisms and to have no functions in higher organisms. However, recently, D-amino acids were discovered also in eukaryotes, including mammals and their physiological roles have been clarified. D-Serine occurs in mammalian brains and serves as an intrinsic coagonist of the N-methyl-D-aspartate (NMDA) glutamate receptors and modulates brain functions. D-Serine is considered to be synthesized by mammalian-type serine racemase and degraded by D-amino acid oxidase, however the detailed metabolic pathway remains unclear. In this research project, we studied the metabolic pathways of D-amino acids in fusion yeast, Schoizosaccharomyces pombe, cellular slime mold, Dyctiostelium discoideum, and silkworm, Bombyx mori. The former two organisms contain mammalian-type serine racemase and D-amino acid oxidase. The S. pombe and D. discoideum serine racemases exhibit the similar properties to those of the mammalian enzyme, for example they catalyze the dehydrataion of D-and L-serine as well as the racemization. To understand the detailed reaction mechanism, we carried out the X-ray crystallography of the yeast serine racemase. We partially purified the silkworm serine racemase and demonstrated that the enzyme catalyzes dominantly racemization and no dehydratation of D-and L-serine. The silkworm serine racemase is the real racemase in this context. During the study of the S. pome D-amino acid oxidase, we found that the enzyme is unique in acting on acidic amino acids. We also found that the budding yeast, Saccharomyces cerevisiae, contains pyridoxal phosphate-dependent D-serine dehydratase, of which primary structure is completely different from that of the bacterial enzymes.

D-氨基酸被认为只存在于低等生物中，在高等生物中没有功能。然而，最近，D-氨基酸也被发现在真核生物中，包括哺乳动物和它们的生理作用已经澄清。D-丝氨酸存在于哺乳动物脑中，作为N-甲基-D-天冬氨酸（NMDA）谷氨酸受体的内在促凝剂，调节脑功能。D-丝氨酸被认为是由丝氨酸消旋酶合成并被D-氨基酸氧化酶降解的，但具体的代谢途径尚不清楚。本研究以融合酵母、粟酒裂殖酵母、细胞黏菌和家蚕为研究对象，研究了D-氨基酸在4种细胞中的代谢途径。前两种菌含有丝氨酸消旋酶和D-氨基酸氧化酶。色葡萄pombe和D. discoideum丝氨酸消旋酶表现出与哺乳动物酶相似的性质，例如它们催化D-和L-丝氨酸的消旋以及外消旋。为了了解详细的反应机理，我们进行了酵母丝氨酸消旋酶的X射线晶体学。我们对家蚕丝氨酸消旋酶进行了部分纯化，证明该酶主要催化D-和L-丝氨酸的消旋，而不催化D-和L-丝氨酸的消旋。在这种情况下，家蚕丝氨酸消旋酶是真实的消旋酶。在对S.在梨果D-氨基酸氧化酶中，我们发现该酶是唯一作用于酸性氨基酸的酶。我们还发现，芽殖酵母，酿酒酵母，含有磷酸吡哆醛依赖的D-丝氨酸脱氢酶，其一级结构是完全不同的细菌酶。

项目成果

Subcellular localization of a germiantion-specifis cortex-lytic enzyme, SleB, of Bacilli during sporulation

孢子形成过程中芽孢杆菌萌发特异性皮质裂解酶 SleB 的亚细胞定位

• 发表时间: 2006
• 期刊: Genes ＆ Genetic Systems 81・3
• 作者: Masayama;A.
• 通讯作者: A.

Physiological role of D-amino acid-N-acetyltransferase of Saccharomyces cerevisiae : detoxification of D-arnino acids

酿酒酵母 D-氨基酸-N-乙酰转移酶的生理作用：D-氨基酸解毒

• 发表时间: 2006
• 期刊: Archives of Microbiology 185・1
• 作者: Yow;Geok-Yong
• 通讯作者: Geok-Yong

D-Amino acid-N-acetyltransferase of. Saccharomyces cerevisiae : A novel member of Gcn5-related N-acetyltransferase (GNAT) superfa mily encoded by HPA3

D-氨基酸-N-乙酰转移酶。

• 发表时间: 2004
• 期刊: Archives of Microbiology 182・5
• 作者: Yow;Geok-Yong
• 通讯作者: Geok-Yong

A Novel Lipolytic Enzyme, YcsK (LipC), Located in the Spore Coat of Bacillus subtilis, Is Involved in Spore Germination

• DOI: 10.1128/jb.01527-06
• 发表时间: 2007-01
• 期刊: Journal of Bacteriology
• 影响因子: 3.2
• 作者: Atsushi Masayama;Ritsuko Kuwana;H. Takamatsu;H. Hemmi;T. Yoshimura;K. Watabe;R. Moriyama

D-Amino acid-N-acetyltransferase of Saccharomyces cerevisiae : A novel member of Gcn5-related N-acetyltransferase (GNAT) superfamily encoded by HPA3

酿酒酵母 D-氨基酸-N-乙酰转移酶：由 HPA3 编码的 Gcn5 相关 N-乙酰转移酶 (GNAT) 超家族的新成员

• 发表时间: 2004
• 期刊: Archives of Microbiology 182・5
• 作者: Yow;Geok-Yong
• 通讯作者: Geok-Yong