Structural redesign and stabilization of the overlapping tandem beta-turns of RNA polymerase II.
Structural redesign and stabilization of the overlapping tandem beta-turns of RNA polymerase II.
复制标题
RNA 聚合酶 II 重叠串联 β 转角的结构重新设计和稳定性。
DOI：
10.1111/j.1399-3011.1996.tb01354.x
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Long,EC
中科院分区：
文献类型：
--
作者：
Dobbins,JR;Murali,N;Long,EC
代表 RNA 聚合酶 II (Tyr-Ser-Pro-Thr-Ser-Pro-Ser-Tyr-NH2, 1) 羧基末端结构域 (CTD) 单个重复单元的肽包含重叠的 Ser-Pro-Xaa-Xaa β 转角形成位点，这使得它们的整体结构与抗肿瘤 DNA 双嵌入剂的喹喔啉类成员非常相似。我们通过替换 Gly 或 D-Ala 在每个 β 转角单元的 i+2 个位置上修改了这个天然序列，试图在水溶液中预组织这个结构。 CD 和 NMR 光谱研究证实，每个取代肽中都存在 II 型 β 转角，而天然序列则包含相对较少的转角结构。此外，对单取代肽的检查表明，氨基末端 Ser-Pro-Xaa-Xaa 位点内 β 转角结构数量的增加也增加了羧基末端（未修饰）Ser-Pro-Xaa-Xaa 位点中 β 转角结构的形成；相比之下，羧基末端位点的取代并不影响肽其余部分的结构。总的来说，这些结果表明所形成的结构可以提供独特的功能。用于构建新型 DNA 交互双嵌入剂的预组织连接体。 © 蒙克斯加德 1996。
Peptides representing single repeat units of the carboxy‐terminal domain (CTD) of RNA polymerase II (Tyr‐Ser‐Pro‐Thr‐Ser‐Pro‐Ser‐Tyr‐NH2, 1) contain overlapping Ser‐Pro‐Xaa‐Xaa β‐turn forming sites which permit their overall structure to closely resemble members of the quinoxaline class of antitumor DNA bisintercalators. We have modified this native sequence at thei+2positions of each β‐turn unit by substituting Gly or D‐Ala in an attempt to preorganize this structure in aqueous solution. CD and NMR spectroscopic investigations confirmed the presence of type II β‐turns within each of the substituted peptides in contrast to the native sequence which contains a relatively low population of turn structure. In addition, an examination of singly substituted peptides suggests that an increase in the population of β‐turn structure within the amino‐terminal Ser‐Pro‐Xaa‐Xaa site also increased the formation of β‐turn structure in the carboxy‐terminal (unmodified) Ser‐Pro‐Xaa‐Xaa site; in comparison, substitution in the carboxy‐terminal site did not influence structure in the remaining portion of the peptide. Overall, these results suggest that the structures formed could provide unique. preorganized linkers for the construction of novel DNA‐interactive bisintercalators. © Munksgaard 1996.