3'-NADP and 3'-NAADP, Two Metabolites Formed by the Bacterial Type III Effector AvrRxo1.

3'-NADP and 3'-NAADP, Two Metabolites Formed by the Bacterial Type III Effector AvrRxo1.
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DOI:
10.1074/jbc.m116.751297
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发表时间:
2016-10-28
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Meinhart A
Meinhart A
中科院分区:
其他
文献类型:
--
作者:
Schuebel F;Rocker A;Edelmann D;Schessner J;Brieke C;Meinhart A

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细菌病原体将效应蛋白的武库注射到宿主细胞或其附近以增加毒力。通常使用的自上而下的方法推断从宿主的表型的单个效应蛋白的毒性机制,往往受到不同效应物的多个靶标以及它们的多效性效应的阻碍。在这里,我们描述了我们自下而上的方法,表明植物病原体的细菌III型效应子AvrRxo 1是一种真正的磷酸转移酶,通过在腺苷3′-羟基上磷酸化烟酰胺/烟酸腺嘌呤二核苷酸产生两种新的代谢产物。AvrRxo 1的两种产物,3′-NADP和3′-烟酸腺嘌呤二核苷酸磷酸(3′-NAADP),与普遍存在的辅酶2′-NADP和钙动员剂2′-NAADP实质上不同。有趣的是,3′-NADP和3′-NAADP以前被用作抑制剂或信号分子,但迄今为止被认为是“人工”化合物。我们的研究结果现在需要转变对3′-磷酸化NAD衍生物的生物学重要性的思考。
An arsenal of effector proteins is injected by bacterial pathogens into the host cell or its vicinity to increase virulence. The commonly used top-down approaches inferring the toxic mechanism of individual effector proteins from the host's phenotype are often impeded by multiple targets of different effectors as well as by their pleiotropic effects. Here we describe our bottom-up approach, showing that the bacterial type III effector AvrRxo1 of plant pathogens is an authentic phosphotransferase that produces two novel metabolites by phosphorylating nicotinamide/nicotinic acid adenine dinucleotide at the adenosine 3′-hydroxyl group. Both products of AvrRxo1, 3′-NADP and 3′-nicotinic acid adenine dinucleotide phosphate (3′-NAADP), are substantially different from the ubiquitous co-enzyme 2′-NADP and the calcium mobilizer 2′-NAADP. Interestingly, 3′-NADP and 3′-NAADP have previously been used as inhibitors or signaling molecules but were regarded as “artificial” compounds so far. Our findings now necessitate a shift in thinking about the biological importance of 3′-phosphorylated NAD derivatives.