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-氨基酸曾被认为仅存在于低等生物中，而在高等生物中没有功能。然而，最近，在包括哺乳动物在内的真核生物中也发现了D-氨基酸，并且它们的生理作用已被阐明。 D-丝氨酸存在于哺乳动物大脑中，作为 N-甲基-D-天冬氨酸 (NMDA) 谷氨酸受体的内在共激动剂并调节大脑功能。 D-丝氨酸被认为是由哺乳动物型丝氨酸消旋酶合成并被D-氨基酸氧化酶降解，但详细的代谢途径仍不清楚。在这个研究项目中，我们研究了融合酵母、Schoizosaccharomyces pombe、细胞粘菌、Dyctiostelium discoideum 和家蚕 Bombyx mori 中 D-氨基酸的代谢途径。前两种生物含有哺乳动物型丝氨酸消旋酶和D-氨基酸氧化酶。 S. pombe 和 D. discoideum 丝氨酸消旋酶表现出与哺乳动物酶类似的特性，例如它们催化 D-和 L-丝氨酸的脱水以及外消旋化。为了了解详细的反应机制，我们对酵母丝氨酸消旋酶进行了 X 射线晶体学分析。我们部分纯化了蚕丝氨酸消旋酶，并证明该酶主要催化外消旋化，并且不会导致 D-和 L-丝氨酸脱水。蚕丝氨酸消旋酶是本文中真正的消旋酶。在对梨果D-氨基酸氧化酶的研究中，我们发现该酶在作用于酸性氨基酸方面具有独特性。我们还发现芽殖酵母酿酒酵母含有磷酸吡哆醛依赖性D-丝氨酸脱水酶，其一级结构与细菌酶的一级结构完全不同。

项目成果

Expression of germination-related enzymes, CspA, CspB, CspC, SIeC, and SIeM, of Clostridium perfringens S40 in the mother cell compartment of sporulating cells

产气荚膜梭菌 S40 发芽相关酶 CspA、CspB、CspC、SIeC 和 SIeM 在孢子细胞母细胞室中的表达

• 发表时间: 2006
• 作者: Masayama; A.
• 通讯作者: A.

Expression of germination-related enzym s, CspA, CspB, CspC, SleC, and SIeM, of Clostridium perfringens S40 in the mother cell compartment of sporulating cells

产气荚膜梭菌 S40 发芽相关酶 CspA、CspB、CspC、SleC 和 SIeM 在孢子细胞母细胞区室中的表达

• 作者: Masayama; A.
• 通讯作者: A.

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
• 作者: Yow; Geok
• 通讯作者: Geok

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

一种新型脂肪分解酶 YcsK (LipC)，位于枯草芽孢杆菌孢子衣中，参与孢子萌发

• DOI: 10.1128/jb.01527-06
• 发表时间: 2007-01-12
• 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
• 通讯作者: R. Moriyama

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
• 作者: Yow; Geok
• 通讯作者: Geok