Structure of a DNA - Porphyrin complex
Structure of a DNA - Porphyrin complex
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DOI：
10.1021/bi952443z
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发表时间：
1996-03-05
期刊：
影响因子：
2.9
通讯作者：
Williams, LD
中科院分区：
文献类型：
--
作者：
Lipscomb, LA;Zhou, FX;Williams, LD
我们报道了一个配合物的2.4埃分辨X射线结构，其中一个小分子从DNA螺旋堆栈中翻转出一个碱基，小分子是一个金属卟啉，CuTMPyP4[铜(II)中位四(N-甲基-4-吡啶)卟啉]，DNA是一个六聚体双链，[d(CGATCG)](2)。铜原子靠近螺旋轴的卟啉体系位于螺旋堆栈内，通过5‘TCG 3’的C和G之间的正常插层和5‘CGA 3’的C挤压键合。DNA形成一个扭曲的右旋螺旋，只有四个正常的交叉链Watson-Crick碱基对，在DNA的每个凹槽中都有两个吡啶环，该络合物似乎通过吡啶环上带正电的氮原子和DNA上带负电的磷酸氧原子之间的静电相互作用而广泛稳定。良好的静电相互作用似乎将卟啉吸引到双链内部，抵消了吡啶环和DNA主链之间不利的空间碰撞。这些吡啶-主链的碰撞使DNA沿其轴线延伸，阻止了在复合体内部形成van der Waals堆积接触，堆积接触是DNA稳定性的主要贡献因素。卟啉复合体中不寻常地缺乏范德华堆叠接触，破坏了DNA双链的稳定，降低了局部熔化的能量成本。因此，碱基的挤出似乎是由吡啶-DNA空间碰撞促进的。
We report the 2.4 Angstrom resolution X-ray structure of a complex in which a small molecule flips a base out of a DNA helical stack, The small molecule is a metalloporphyrin, CuTMPyP4 [copper(II) meso-tetra(N-methyl-4-pyridyl)porphyrin] and the DNA is a hexamer duplex, [d(CGATCG)](2). The porphyrin system, with the copper atom near the helical axis, is located within the helical stack, The porphyrin binds by normal intercalation between the C and G of 5' TCG 3' and by extruding the C of 5' CGA 3'. The DNA forms a distorted right-handed helix with only four normal cross-strand Watson-Crick base pairs, Two pyridyl rings are located in each groove of the DNA, The complex appears to be extensively stabilized by electrostatic interactions between positively charged nitrogen atoms of the pyridyl rings and negatively charged phosphate oxygen atoms of the DNA. Favorable electrostatic interactions appear to draw the porphyrin into the duplex interior, offsetting unfavorable steric clashes between the pyridyl rings and the DNA backbone. These pyridyl-backbone clashes extend the DNA along its axis and preclude formation of van der Waals stacking contacts in the interior of the complex, Stacking contacts are the primary contributor to stability of DNA. The unusual lack of van der Waals stacking contacts in the porphyrin complex destabilizes the DNA duplex and decreases the energetic cost of local melting. Thus extrusion of a base appears to be facilitated by pyridyl-DNA steric clashes.