Structural basis of novel quadruplex-duplex switching of nucleic acids

新型核酸四链体-双链体转换的结构基础

• 批准号: 09680648
• 负责人: KATAHIRA Masato
• 金额: $ 2.11万
• 依托单位: Yokohama National University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680648/
• 关键词: DNA; RNA; NMR; quadruplex; duplex; telomere; protein; antitumor drug; 金属イオン; ドラッグ; リボザイム

The novel quadruplex and duplex structures of d(GGAGGA), formed in the presence and absence of potassium ions, respectively, were determined by NMR.It is notable that the duplex structure is composed exclusively of non-standard G : G and A : A basepairs.It was found for the first time that the RNA-binding protein, hnRNP D0 has the ability to transform the quadruplex structure to a single-stranded form. The structures and interactions with RNA of hnRNP DO and the related protein, Musashi1, were determined by NMR.It was suggested that this unique activity may be related to the maintenance of the telomere.The structure of the novel antitumor drug, UCH9, complexed with DNA was determined by NMR.The B-form to A-form structural transition caused by drug-binding was identified, and its biological significance was implied.

d（GGAGGA）在钾离子存在和不存在的情况下分别形成了新的四联和双联结构。值得注意的是，双工结构完全由非标准G: G和A: A碱基对组成。首次发现rna结合蛋白hnRNP D0具有将四重结构转化为单链结构的能力。hnRNP DO及其相关蛋白Musashi1的结构和与RNA的相互作用通过NMR测定。有人认为这种独特的活性可能与端粒的维持有关。新型抗肿瘤药物UCH9与DNA配合物的结构经核磁共振测定。鉴定了药物结合引起的b型到a型的结构转变，并暗示了其生物学意义。

项目成果

Katahira他: "Structural characterization of a DNA duplex modeled on the polypurine tract"Nucleosides & Nucleotides. 17. 831-841 (1998)

Katahira 等人：“基于多嘌呤束的 DNA 双链体的结构表征”核苷与核苷酸 17. 831-841 (1998)。

Sakamoto.T.: "Properties of a hammerhead ribozyme with deletion of stemII"J. Biochem.. 121. 288-294 (1997)

Sakamoto.T.：“删除茎 II 的锤头核酶的特性”J。

Kobayashi,S: "The structures of nucleic acids composed exclusively of non-standard base pairs"Nucleic Acids Symp Ser.. 37. 103-104 (1997)

Kobayashi,S：“仅由非标准碱基对组成的核酸的结构”Nucleic Acids Symp Ser.. 37. 103-104 (1997)

Sakamoto, T.: "Properties of hepatitis dalta virus ribozyme, which consists of three RNA oligomer strands" J.Biochem.121. 1123-1128 (1997)

Sakamoto, T.：“由三个 RNA 寡聚链组成的肝炎病毒核酶的特性”J.Biochem.121。

Katahira他: "Structure backbone dynamics and interactions with RNA of the c-terminal RNA-binding domain of Musashi1"J. Mol. Biol.. 287. 314-330 (1999)

Katahira 等人：“Musashi1 的 c 末端 RNA 结合结构域的结构主链动力学及其与 RNA 的相互作用”J. Mol.. 287. 314-330 (1999)