CHARACTERIZATION OF MAMMALIAN ADP-RIBOSLYTRANSFERASES
CHARACTERIZATION OF MAMMALIAN ADP-RIBOSLYTRANSFERASES
批准号:
2576748
负责人:
J MOSS
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
单ADP核糖基化,一种蛋白质翻译后修饰,
其中NAD的ADP-核糖部分被转移到蛋白质,
导致某些细菌毒素的毒性(例如,霍乱
毒素、百日咳毒素)。 NAD:精氨酸ADP-核糖基转移酶克隆
来自人和兔骨骼肌以及来自小鼠淋巴瘤细胞(Yac,
1 ADP-核糖基转移酶),是糖基磷脂酰肌醇(GPI)-
锚定并具有类似的酶和物理性质。 第二
从小鼠淋巴瘤细胞中克隆了ADP-核糖基转移酶(Yac-2),
其性质不同于先前鉴定的真核生物
转移酶 该基因的核苷酸和推导的氨基酸序列
Yac-1和Yac-2转移酶分别为58%和33%相同。 的
Yac-2蛋白是膜结合的,但与Yac-1酶不同,
是GPI锚定的 Yac-1和Yac-2酶,表示为
谷胱甘肽-S-转移酶融合蛋白在E.大肠杆菌,用于
比较它们的ADP-核糖基转移酶和NAD糖水解酶活性。
使用胍丁胺作为ADP-核糖受体,
主要是ADP-核糖基转移酶,而转移酶和NAD
重组Yac-2蛋白的糖水解酶活性相似。
推导的Yac-2转移酶的氨基酸序列包含
几种细菌毒素和哺乳动物毒素共有的共有区
转移酶和NAD糖水解酶,与以下假设一致,
在ADP-1和ADP-2中,NAD的结合和催化有一个共同的机制,
核糖基转移酶。
英文摘要
Mono-ADP-ribosylation, a posttranslational modification of proteins in
which the ADP-ribose moiety of NAD is transferred to proteins, is
responsible for the toxicity of some bacterial toxins (e.g., cholera
toxin, pertussis toxin). NAD:arginine ADP-ribosyltransferases cloned
from human and rabbit skeletal muscle and from mouse lymphoma cells (Yac-
1 ADP-ribosyltransferase), are glycosylphosphatidylinositol (GPI)-
anchored and have similar enzymatic and physical properties. A second
ADP-ribosyltransferase (Yac-2) was cloned from mouse lymphoma cells,
which differs in properties from the previously identified eukaryotic
transferases. The nucleotide and deduced amino acid sequences of the
Yac-1 and Yac-2 transferases are 58 and 33% identical, respectively. The
Yac-2 protein is membrane-bound but, unlike the Yac-1 enzyme, appears not
to be GPI-anchored. The Yac-1 and Yac-2 enzymes, expressed as
glutathione-S-transferase fusion proteins in E. coli, were used to
compare their ADP-ribosyltransferase and NAD glycohydrolase activities.
Using agmatine as the ADP-ribose acceptor, the Yac-1 enzyme was
predominantly an ADP-ribosyltransferase, whereas the transferase and NAD
glycohydrolase activities of the recombinant Yac-2 protein were similar.
The deduced amino acid sequence of the Yac-2 transferase contained
consensus regions common to several bacterial toxin and mammalian
transferases and NAD glycohydrolases, consistent with the hypothesis that
there is a common mechanism of NAD binding and catalysis among ADP-
ribosyltransferases.
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批准号:2441409
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J MOSS
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依托单位:
REGULATION OF CYCLIC NUCLEOTIDE METABOLISM
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批准号:3857979
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资助金额:$0.0万
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资助金额:$0.0万
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财政年份:--
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批准号:6162671
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海外基金