Identification of Gangliosides as Inhibitors of ADP-ribosyltransferases of Pertussis Toxin and Exoenzyme C3 from Clostridium botulinum(*)

Identification of Gangliosides as Inhibitors of ADP-ribosyltransferases of Pertussis Toxin and Exoenzyme C3 from Clostridium botulinum(*)
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鉴定神经节苷脂作为百日咳毒素 ADP-核糖基转移酶抑制剂和肉毒杆菌外切酶 C3(*)

DOI:
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发表时间:
1995
影响因子:
4.8
通讯作者:
S. Furuyama
S. Furuyama
中科院分区:
生物学2区
文献类型:
--
作者:
M. Hara;Y. Hirabayashi;F. Irie;B. Syuto;K. Moriishi;H. Sugiya;S. Furuyama

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我们先前已经报道了牛脑中存在对百日咳毒素(PT)催化的GTP结合蛋白的ADP-核糖基化的内源性抑制活性(Hara-Yokoyama,M.,和Furuyama,S.(1989)Biochem. Biophys. Res. Commun. 160,67-71)。在本研究中,我们确定了抑制剂作为神经节苷脂。各种神经节苷脂的筛选结果表明,GQ 1b α最有效地抑制了PT全酶和催化亚基的ADP-核糖基转移酶活性。GQ 1b α是一种神经节苷脂,新鉴定为胆碱能神经元特异性抗体抗Chol-1α识别的抗原之一(Hirabayashi,Y.,Nakao,T.,Irie,F.,惠特克副总裁Kon,K.,和Ando,S.(1992)J.Biol.Chem.267,12973-12978)。GQ 1b α还抑制PT催化的NAD+糖水解。与PT活性不同,由C型肉毒梭菌C3外切酶催化的ADP-核糖基化和NAD+糖水解被GT 1b和GQ 1b抑制。由PT或C3外切酶催化的ADP-核糖基化不被神经酰胺、半乳糖苷或唾液酸抑制。除了神经节苷脂对ADP-核糖基化的抑制作用,神经节苷脂作为NAD+代谢调节剂的重要性进行了讨论。
We have previously reported the presence of an endogenous inhibitory activity in bovine brain for the ADP-ribosylation of GTP-binding proteins catalyzed by pertussis toxin (PT) (Hara-Yokoyama, M., and Furuyama, S.(1989) Biochem. Biophys. Res. Commun. 160, 67-71). In the present study, we identified the inhibitor as a ganglioside. The screening of various gangliosides revealed that GQ1bα most effectively inhibited the ADP-ribosyltransferase activities of both the holoenzyme and the catalytic subunit of PT. GQ1bα is a ganglioside newly identified as one of the antigens recognized by the cholinergic neuron-specific antibody, anti-Chol-1α (Hirabayashi, Y., Nakao, T., Irie, F., Whittaker, V.P., Kon, K., and Ando, S.(1992) J. Biol. Chem. 267, 12973-12978). GQ1bα also inhibited the PT-catalyzed NAD+ glycohydrolysis. Unlike PT activity, the ADP-ribosylation and the NAD+ glycohydrolysis catalyzed by the C3 exoenzyme from Clostridium botulinum type C were inhibited by GT1b and GQ1b. The ADP-ribosylation catalyzed by either PT or the C3 exoenzyme was not inhibited by ceramide, galactocerebroside, or sialic acid. In addition to the inhibitory action of gangliosides on ADP-ribosylation, the importance of gangliosides as regulators of NAD+ metabolism is discussed.
DOI: 10.1073/pnas.89.1.118
发表时间: 1992
影响因子: 11.1
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影响因子: 5
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