Bennett M, Krah A, Wien F, Garman E, McKenna R, Sanderson M, Neidle S
The Randall Institute, Department of Biomedical Sciences, King's College London, United Kingdom.
Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9476-81. doi: 10.1073/pnas.160271897.
The crystal structure of a B-type DNA hexanucleotide duplex complexed with the porphyrin molecule nickel-[tetra-N-methyl-pyridyl] porphyrin has been solved by multiwavelength anomalous diffraction phasing and refined to an R factor of 11.5% at a resolution of 0.9 A. The structure has been solved and refined as two crystallographically independent duplexes, stacked end to end. Contrary to expectation, the porphyrin molecule is not intercalated into the duplex but is stacked onto the ends of the two-duplex stack. The porphyrin molecule is highly buckled as a consequence of the nickel coordination, which produces large changes in local DNA structure. A second mode of porphyrin binding is apparent as a consequence of crystal packing, which places the ligand in the minor groove of an adjacent duplex. This structure thus provides, to our knowledge, the first atomic visualization of minor-groove binding for a porphyrin molecule. The geometry of groove binding provides a ready explanation for porphyrin-induced DNA strand cleavage at deoxyribose residues.
通过多波长反常衍射相位法解析了与卟啉分子镍-[四-N-甲基-吡啶基]卟啉复合的B型DNA六核苷酸双链体的晶体结构，并在0.9埃分辨率下精修至R因子为11.5%。该结构被解析并精修为两个晶体学独立的双链体，首尾相连堆积。与预期相反，卟啉分子并未插入双链体中，而是堆积在两个双链体堆叠的末端。由于镍配位，卟啉分子高度弯曲，这导致局部DNA结构发生重大变化。由于晶体堆积，卟啉结合的第二种模式很明显，即配体位于相邻双链体的小沟中。据我们所知，该结构首次提供了卟啉分子在小沟结合的原子可视化。沟结合的几何结构为卟啉诱导的脱氧核糖残基处的DNA链断裂提供了现成的解释。
