大肠杆菌核酸内切酶IV对α-N-甲基甲酰胺嘧啶异构体的选择性切割
Selective Incision of the alpha-N-Methyl-Formamidopyrimidine Anomer by Escherichia coli Endonuclease IV.
作者信息
Christov Plamen P, Banerjee Surajit, Stone Michael P, Rizzo Carmelo J
机构信息
Departments of Chemistry and Biochemistry, Center in Molecular Toxicology, Vanderbilt University, VU Station B 351822, Nashville, N 37235-1822, USA.
出版信息
J Nucleic Acids. 2010 Jul 25;2010:850234. doi: 10.4061/2010/850234.
Formamidopyrimidines (Fapy) lesions result from ring opening of the imidazole portion of purines. Fapy lesions can isomerize from the natural beta-anomeric stereochemistry to the alpha-configuration. We have unambiguously demonstrated that the alpha-methyl-Fapy-dG (MeFapy-dG) lesion is a substrate for Escherichia coli Endonuclease IV (Endo IV). Treatment of a MeFapy-dG-containing 24 mer duplex with Endo IV resulted in 36-40% incision. The catalytic efficiency of the incision was comparable to that of alpha-dG in the same duplex sequence. The alpha- and beta-MeFapy-dG anomers equilibrate to ~21 : 79 ratio over ~3 days. Related studies with a duplex containing the alpha-Fapy-dG lesion derived from aflatoxin B(1) epoxide (alpha-AFB-Fapy-dG) showed only low levels of incision. It is hypothesized that the steric bulk of the aflatoxin moiety interferes with the binding of the substrate to Endo IV and the incision chemistry.
甲酰胺嘧啶（Fapy）损伤是由嘌呤咪唑部分的开环产生的。Fapy损伤可从天然的β-异头立体化学异构化为α-构型。我们已经明确证明，α-甲基-Fapy-dG（MeFapy-dG）损伤是大肠杆菌核酸内切酶IV（Endo IV）的底物。用Endo IV处理含有MeFapy-dG的24聚体双链体导致36 - 40%的切口。在相同双链体序列中，切口的催化效率与α-dG相当。α-和β-MeFapy-dG异头物在约3天内达到约21 : 79的平衡比例。对含有由黄曲霉毒素B(1)环氧化物衍生的α-Fapy-dG损伤（α-AFB-Fapy-dG）的双链体的相关研究仅显示出低水平的切口。据推测，黄曲霉毒素部分的空间位阻会干扰底物与Endo IV的结合以及切口化学过程。
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