Okazaki I J, Kim H J, Moss J
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Adv Exp Med Biol. 1997;419:129-36. doi: 10.1007/978-1-4419-8632-0_15.
Mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases, is a posttranslational modification of proteins in which the ADP-ribose moiety of NAD is transferred to an acceptor protein(arginine). Several of the bacterial toxin ADP-ribosyltransferases have been well characterized in their ability to alter cellular metabolism. It has been postulated that these bacterial toxins mimic the actions of transferases from mammalian cells. We have cloned and characterized ADP-ribosyltransferases from rabbit and human skeletal muscle, and mouse lymphocytes. The muscle transferases are glycosylphosphatidylinositol (GPI)-anchored proteins that are conserved among species. Two distinct transferases, termed Yac-1 and Yac-2 were cloned from mouse lymphoma (Yac-1) cells. The Yac-1 transferase, like the muscle enzymes, is a GPI-linked exoenzyme. The Yac-2 transferase, on the other hand, is membrane-associated but appears not to be GPI-linked. In contrast to Yac-1, the Yac-2 enzyme had significant NAD glycohydrolase activity and may preferentially hydrolyze NAD. The bacterial toxin ADP-ribosyltransferases contain three noncontiguous regions of sequence similarity, which are involved in formation of the catalytic site. Alignment of the deduced amino acid sequences of the mammalian transferases and the rodent RT6 enzymes, along with results from site-directed mutagenesis of the muscle enzyme, are consistent with the notion of a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases.
由ADP-核糖基转移酶催化的单ADP-核糖基化是蛋白质的一种翻译后修饰，其中NAD的ADP-核糖部分转移到受体蛋白（精氨酸）上。几种细菌毒素ADP-核糖基转移酶在改变细胞代谢的能力方面已得到充分表征。据推测，这些细菌毒素模拟了哺乳动物细胞中转移酶的作用。我们已经克隆并表征了来自兔和人骨骼肌以及小鼠淋巴细胞的ADP-核糖基转移酶。肌肉转移酶是糖基磷脂酰肌醇（GPI）锚定蛋白，在物种间保守。从鼠淋巴瘤（Yac-1）细胞中克隆出两种不同的转移酶，称为Yac-1和Yac-2。Yac-1转移酶与肌肉酶一样，是一种GPI连接的外切酶。另一方面，Yac-2转移酶与膜相关，但似乎不是GPI连接的。与Yac-1不同，Yac-2酶具有显著的NAD糖水解酶活性，可能优先水解NAD。细菌毒素ADP-核糖基转移酶包含三个不连续的序列相似区域，它们参与催化位点的形成。哺乳动物转移酶和啮齿动物RT6酶的推导氨基酸序列比对，以及肌肉酶定点诱变的结果，与ADP-核糖基转移酶中NAD结合和催化的共同机制这一概念一致。
