Insights into how protein dynamics affects arylamine N-acetyltransferase catalysis.
Insights into how protein dynamics affects arylamine N-acetyltransferase catalysis.
复制标题
深入了解蛋白质动力学如何影响芳胺 N-乙酰转移酶催化。
DOI：
10.1016/j.bbrc.2009.05.065
复制
发表时间：
2009
影响因子：
3.1
通讯作者：
Walters,KylieJ
中科院分区：
文献类型：
--
作者：
Zhang,Naixia;Walters,KylieJ
芳胺N-乙酰基转移酶（NAT）通过催化芳胺和肼类异生物质的N-乙酰化来解毒芳胺和肼类异生物质，这阻止了它们的生物活化。在这里，我们揭示了结构动力学如何影响NAT蛋白的功能。我们的数据表明，有多种构象在仓鼠NAT 2的催化腔中，在毫秒级的时间尺度上交换，使NAT能够容纳不同大小的底物。跨越N177-L180和D285-F288的区域在哺乳动物NAT中形成独特的结构，具有纳秒时间尺度上的固有运动。根据我们的NMR XNOE数据，后一段在底物结合时的运动变得更加受限。这种更大的刚性似乎源于与基材的相互作用。最后，NAT乙酰化被认为可以保护这些酶免于泛素化。我们对仓鼠NAT 2的催化活性状态的NMR数据表明，由其乙酰化引起的结构重排可能有助于这种保护。
Arylamine N-acetyltransferases (NATs) detoxify arylamines and hydrazine xenobiotics by catalyzing their N-acetylation, which prevents their bioactivation. Here, we reveal how structural dynamics impact NAT protein function. Our data suggest that there are multiple conformations in the catalytic cavity of hamster NAT2 that exchange on the millisecond time scale and enable NATs to accommodate substrates of varying size. The regions spanning N177–L180 and D285–F288, which form unique structures in mammalian NATs, possess inherent motions on the nanosecond time scale. The latter segment becomes more restricted in its motions upon substrate binding according to our NMR XNOE data. This greater rigidity appears to stem from interactions with the substrate. Finally, NAT acetylation has been suggested to protect these enzymes from ubiquitination. Our NMR data on a catalytically active state of hamster NAT2 suggest that structural rearrangements caused by its acetylation might contribute to this protection.