Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Biophys Chem. 2010 Jun;149(1-2):34-9. doi: 10.1016/j.bpc.2010.03.014. Epub 2010 Mar 27.
Distamycin A (Dst) is an antibiotic which binds to the minor groove of double-stranded DNA at A/T-rich regions. We have examined the affinity and mode of Dst binding to DNA duplexes containing a conserved A/T core and variable terminal A/T regions by using circular dichroism spectroscopy. The observed circular dichroism spectra were analyzed by singular value decomposition and fitted to a two-step binding model. The result clearly shows a correlation between the affinity for Dst and the preference for Dst-DNA 1:1 binding over 2:1 binding. The A/T stretches that prefer 1:1 binding form high-affinity 1:1 complexes, whereas those preferring 2:1 binding form stable 2:1 complex with low overall affinities. The terminal A/T residues of the Dst binding region play an important role in the stabilization/destabilization of the 1:1 and 2:1 complexes, resulting in a terminal residue-dependent variation of the binding affinity and the binding mode preference.
道他霉素 A（Dst）是一种抗生素，可与富含 A/T 的双链 DNA 的小沟结合。我们通过使用圆二色性光谱检查了含有保守 A/T 核心和可变末端 A/T 区域的 DNA 双链与 Dst 的亲和力和结合模式。观察到的圆二色性光谱通过奇异值分解进行分析，并拟合到两步结合模型中。结果清楚地表明，Dst 的亲和力与 Dst-DNA 1:1 结合相对于 2:1 结合的偏好之间存在相关性。优先形成高亲和力 1:1 复合物的 A/T 延伸，而优先形成 2:1 复合物的 A/T 延伸则形成具有低整体亲和力的稳定 2:1 复合物。Dst 结合区域的末端 A/T 残基在 1:1 和 2:1 复合物的稳定/不稳定中起重要作用，导致结合亲和力和结合模式偏好的末端残基依赖性变化。
