从假单胞菌的动力学分析L-ornithine transcarbamoylase savastanoi pv。phaseolicola过渡态类似物抗的δ- (R) - N (N ' -sulfodiaminophosphinyl) -L-ornithine。

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邓普顿医学博士,莱因哈特洛杉矶,煤灰,米切尔再保险,克莱兰德WW

从假单胞菌的动力学分析L-ornithine transcarbamoylase savastanoi pv。phaseolicola过渡态类似物抗的δ- (R) - N (N ' -sulfodiaminophosphinyl) -L-ornithine。

生物化学。2005年3月22日,44(11):4408 - 15所示。

PubMed ID

15766270 (在PubMed

]

文摘

(R) - N(δ)- (N ' -Sulfodiaminophosphinyl) -L-ornithine (PSorn)是植物毒素的活性成分,称为phaseolotoxin,由假单胞菌savastanoi pv。phaseolicola。PSorn作为强有力的过渡态(TS)抑制剂的鸟氨酸transcarbamoylase (OTCase,提到过2.1.3.3)结合OTCase从大肠杆菌(ARGI)离解常数为1.6点。而抑制OTCase会导致精氨酸营养缺陷型,p . savastanoi pv。phaseolicola能够合成毒素而在基本培养基生长。这是通过第二个基因编码的表达在毒素生产OTCase活动不是由PSorn抑制(ROTCase)。ROTCase其他OTCases同源,但替换关键守恒的氨基酸,特别是那些在[氨基甲酰磷酸(CP)结合位点和鸟氨酸绑定“SMG”循环。这表明,CP的拓扑结合位点和关闭ROTCase SMG循环可能会有所不同。稳态动力学表明,ROTCase有序机制,和(13)C动力学同位素效应(IE) CP表明它是第一个底物结合。然而,不像其他OTCases,有一个随机元素的机制自第二次衬底鸟氨酸(内在的)不能完全抑制IE团结。 The most striking difference with ROTCase is the reduction of k(cat) to between 1% and 2% of other OTCases. This is consistent with the large IE that ROTCase exhibits (3.4%) at near-zero Orn. These results suggest that the chemistry of the reaction is rate limiting for ROTCase. ROTCase has a substrate and inhibitor profile similar to that of other OTCases. The CP binding affinity of ROTCase is diminished when compared with that observed from ARGI, and inhibitors that compete with the CP binding site have K(i) values at least 10-fold higher for ROTCase than for ARGI. Arsenate did not inhibit ROTCase, and bisubstrate and dead-end inhibitors are less effective inhibitors of ROTCase than ARGI. These data suggest that PSorn is unable to bind tightly to either the apo or activated forms of ROTCase at the expense of CP binding and reduced k(cat).

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药物靶点

药物	目标	类	生物	药理作用	行动
鸟氨酸	鸟氨酸carbamoyltransferase,线粒体	蛋白质	人类	未知的	不可用	细节