CLONING AND SEQUENCING OF THIOL-SPECIFIC ANTIOXIDANT FROM MAMMALIAN BRAIN - ALKYL HYDROPEROXIDE REDUCTASE AND THIOL-SPECIFIC ANTIOXIDANT DEFINE A LARGE FAMILY OF ANTIOXIDANT ENZYMES

CLONING AND SEQUENCING OF THIOL-SPECIFIC ANTIOXIDANT FROM MAMMALIAN BRAIN - ALKYL HYDROPEROXIDE REDUCTASE AND THIOL-SPECIFIC ANTIOXIDANT DEFINE A LARGE FAMILY OF ANTIOXIDANT ENZYMES
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DOI:
10.1073/pnas.91.15.7017
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发表时间:
1994-07-19
影响因子:
11.1
通讯作者:
RHEE, SG
RHEE, SG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CHAE, HZ;ROBISON, K;RHEE, SG

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从大鼠脑cDNA文库中分离出一种对应于巯基特异性抗氧化酶(TSA)的cDNA,并使用牛TSA的抗体。该cDNA克隆编码一个能够编码198个残基多肽的开放阅读框。大鼠和酵母TSA蛋白显示出与鼠伤寒沙门氏菌烷基氢过氧化物还原酶的21-kDa组分(AhpC)显著的序列同源性,并且我们已经发现AhpC表现出TSA活性。AhpC和TSA定义了存在于来自所有界的生物体中的>25种不同蛋白质的家族。家族成员之间的相似性在整个序列上延伸,范围在23%和98%之间。AhpC/TSA家族的大多数成员含有两个保守的半胱氨酸。发现编码AhpC/TSA样多肽的基因中至少有八个与编码其他氧化还原酶活性的基因接近,并且几个同源物的表达与致病性相关。我们认为AhpC/TSA家族代表了一类广泛分布的抗氧化酶。我们还报道了由烷基氢过氧化物还原酶的57-kDa组分(AhpF)和硫氧还蛋白还原酶定义的第二个蛋白质家族,已经扩展到包括六个额外的成员,
A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA. The cDNA clone encoded an open reading frame capable of encoding a 198-residue polypeptide. The rat and yeast TSA proteins Show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of >25 different proteins present in organisms from all kingdoms. The similarity among the family members extends over the entire sequence and ranges between 23% and 98% identity. A majority of the members of the AhpC/TSA family contain two conserved cysteines. At least eight of the genes encoding AhpC/TSA-like polypeptides are found in proximity to genes encoding other oxidoreductase activities, and the expression of several Of the homologs has been correlated with pathogenicity. We suggest that the AhpC/TSA family represents a widely distributed class of antioxidant enzymes. We also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by thioredoxin reductase, has expanded to include six additional members,