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信号蛋白中甲硫氨酸残基的可逆性氧化和甲硫氨酸亚砜还原酶
  • 期刊名称:生物物理学报 26: 861-879
  • 时间:0
  • 分类:Q26[生物学—细胞生物学]
  • 作者机构:[1]北京师范大学细胞生物学研究所,北京100875
  • 相关基金:国家自然科学基金项目(30728020 30870580 30970675)
  • 相关项目:单线态氧分子对活细胞G蛋白偶联受体的调控
中文摘要:

含硫氨基酸甲硫氨酸在体内易被胞内、外活性氧氧化为甲硫氨酸-R,S-亚砜。蛋白质肽链中的甲硫氨酸残基被氧化后,蛋白活性发生显著改变,如钙调素与钙调素结合蛋白亲和力的下降、钙离子/钙调素依赖性蛋白激酶Ⅱ的激活、钾离子通道ShC/B失活动力学的改变。多数生物都存在一个msrA基因和1~3个msrB基因,编码两种序列和结构都明显不同的酶:甲硫氨酸亚砜还原酶A(MsrA)和甲硫氨酸亚砜还原酶B(MsrB),分别还原甲硫氨酸-S-亚砜和甲硫氨酸-R-亚砜。两种酶的催化机制基本相同,其活性中心结构互为镜像。两种还原酶分布于体内不同器官及各种亚细胞结构。对于MsrA活性的研究,已有30年的历史,最初主要集中在低等生物,已发现MsrA对于延缓衰老和神经退行性疾病具有重要作用,也是致病菌的主要毒力因子。最近10年对MsrB也进行了系统研究,并取得了重要进展。人们正在逐渐认识到这些酶在细胞信号蛋白分子活性调节中的重要作用。

英文摘要:

Sulphur-containing amino acid methionine is prone to oxidation to methionine-R,S-sulfoxide by reactive oxidative species (ROS) of both intracellular and extracellular origins.Peptide methionine oxidation results in significant changes in protein activity, such as reduced binding affinity for calmodulin-binding by oxidized calmodulin, activation of calcium/calmodulin-dependent protein kinase II, slowed inactivation of potassium channel ShC/B.In most organisms, there exist one msrA gene and one to three msrB genes (msrB1-3), encoding two sequence and structurally-unrelated enzymes:MsrA and MsrB, to reduce methionine-S-sulfoxide and methionine-R-sulfoxide respectively.Both enzymes have rather similar catalytic mechanisms, their reactive center conformations being mirror images.These two reductases are widely distributed in different mammalian organs and subcellular structures.MsrA activity and structure have been investigated in the last thirty years, it playing an important anti-oxidizing role in aging and in neurodegenerative diseases, but is a major virulence factor for pathogenic bacteria.MsrB has also received much attention in the last decade and significant progresses have been made.Roles of these enzymes in regulating activities of signal protein molecules are being gradually recognized.

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