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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells.
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ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells.

机译：ADP-核糖基环化酶产生两个不寻常的腺嘌呤同二核苷酸，对哺乳动物细胞具有细胞毒活性。

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摘要

ADP-ribosyl cyclases are ubiquitous enzymes responsible for synthesis from NAD(+) of the intracellular calcium-releasing signal molecules cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP(+)). Here, we show that cyclases from lower and higher Metazoa also synthesize three adenylic dinucleotides from cADPR and adenine: diadenosine diphosphate and two isomers thereof. These dinucleotides are present and metabolized in mammalian cells and affect intracellular calcium and cell proliferation. The diadenosine diphosphate isomers are naturally occurring nucleotides containing an N-glycosidic bond different from the usual C1'-N9. The identification of these members of the family of NAD(+)-derived, calcium-active nucleotides opens new areas of investigation into their functional cooperation with cADPR and NAADP(+) and into their involvement in the physiology and pathology of calcium-controlled cell functions.
机译：ADP-核糖基环化酶是普遍存在的酶，负责从细胞内钙释放信号分子环ADP-核糖（cADPR）和烟酸腺嘌呤二核苷酸磷酸（NAADP（+））的NAD（+）合成。在这里，我们显示来自较低和较高的后生动物的环化酶还从cADPR和腺嘌呤合成了三个腺苷二核苷酸：二磷酸二腺苷及其两个异构体。这些二核苷酸在哺乳动物细胞中存在并代谢，并影响细胞内钙和细胞增殖。二磷酸腺苷二异构体是天然存在的核苷酸，其核苷酸结构不同于通常的C1'-N9。对这些NAD（+）衍生的钙活性核苷酸家族成员的鉴定，为它们与cADPR和NAADP（+）的功能合作以及它们参与钙控细胞的生理和病理学研究开辟了新的领域功能。

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