CRYSTAL-STRUCTURE OF A BERENIL DODECANUCLEOTIDE COMPLEX - THE ROLE OF WATER IN SEQUENCE-SPECIFIC LIGAND-BINDING
CRYSTAL-STRUCTURE OF A BERENIL DODECANUCLEOTIDE COMPLEX - THE ROLE OF WATER IN SEQUENCE-SPECIFIC LIGAND-BINDING
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DOI：
10.1002/j.1460-2075.1990.tb08242.x
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发表时间：
1990-04-01
期刊：
影响因子：
11.4
通讯作者：
NEIDLE, S
中科院分区：
文献类型：
--
作者：
BROWN, DG;SANDERSON, MR;NEIDLE, S
十二核苷d（CGCGAATTCGCG）与抗锥虫药物berenil之间的完整三维结构已被确定，分辨率为2.5 .ANG。用分子置换法对结构进行求解，得到R因子为0.177。目前已经确定了49个水分子。药物结合在寡核苷酸的5‘ -AAT-3’区。在药物的一端，脒基团与腺嘌呤碱基的N3氢键接触，与AAT的胸腺嘧啶互补。另一个胺基不与DNA直接相互作用。相反，水分子在它们之间起着中介作用。它与氨基氮原子、5'端腺嘌呤碱基的N3和相邻脱氧核糖的环状氧原子形成氢键接触。分子力学计算已经在这个络合物上进行了，药物沿着序列的不同位置。结果表明，观测位置的能量仅比最佳位置高0.8 kcal/mol。这表明该药物在AATT区域存在广泛的能量阱，水分子及其邻近序列将决定其精确定位。讨论了小槽结合的更一般的方面。
The three-dimensional structure of a complete between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 .ANG.. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5''-AAT-3'' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5'' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed.