Department of Chemistry, Center in Molecular Toxicology, Center for Structural Biology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37235, USA.
Biochemistry. 2010 Jul 27;49(29):6155-64. doi: 10.1021/bi100364f.
DNA-protein conjugates are potentially repaired via proteolytic digestion to DNA-peptide conjugates. The latter have been modeled with the amino-terminal lysine of the peptide KWKK conjugated via a trimethylene linkage to the N(2)-dG amine positioned in 5'-d(GCTAGCXAGTCC)-3'.5'-d(GGACTCGCTAGC)-3' (X = N(2)-dG-trimethylene link-KWKK). This linkage is a surrogate for the reversible linkage formed by the gamma-OH-1,N(2)-propanodeoxyguanosine (gamma-OH-PdG) adduct. This conjugated KWKK stabilizes the DNA. Amino acids K(26), W(27), K(28), and K(29) are in the minor groove. The W(27) indolyl group does not intercalate into the DNA. The G(7) N(2) amine and the K(26) N-terminal amine nitrogens are in the trans configuration with respect to the C(alpha) or C(gamma) of the trimethylene tether, respectively. The structure of this DNA-KWKK conjugate is discussed in the context of its biological processing.
DNA-蛋白质缀合物可通过蛋白水解消化修复为 DNA-肽缀合物。后者已通过肽 KWKK 的氨基末端赖氨酸建模，该赖氨酸通过亚甲基连接与 5'-d(GCTAGCXAGTCC)-3' 中 N(2)-dG 胺连接。5'-d(GGACTCGCTAGC)-3'（X = N(2)-dG-亚甲基连接-KWKK）。这种连接是由γ-OH-1,N(2)-丙酰脱氧鸟苷（γ-OH-PdG）加合物形成的可逆连接的替代物。这种缀合的 KWKK 稳定了 DNA。氨基酸 K(26)、W(27)、K(28)和 K(29)位于小沟中。W(27)吲哚基团不会嵌入 DNA 中。G(7)N(2)胺和 K(26)N-末端胺氮分别与亚甲基连接的 C(alpha)或 C(gamma)处于反式构型。该 DNA-KWKK 缀合物的结构在其生物处理的背景下进行了讨论。
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