Goodsell D S, Ng H L, Kopka M L, Lown J W, Dickerson R E
Department of Chemistry and Biochemistry, University of California at Los Angeles 90095, USA.
Biochemistry. 1995 Dec 26;34(51):16654-61. doi: 10.1021/bi00051a013.
An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DNA duplex of sequence CGCGAATTCGCG. The lexitropsin is identical to netropsin except for replacement of the first methylpyrrole ring by methylimidazole, converting a =CH- to =N-. Crystals are isomorphous with those of the DNA dodecamer in the absence of drug. Although the =N- for =CH- substitution was intended to make that locus on the drug molecule compatible with a G.C base pair, electrostatic attraction for the two cationic ends of the drug predominates, and this lexitropsin binds to the same central AATT site as does the parent netropsin. But unlike netropsin, this lexitropsin exhibits end-for-end disorder in the crystal. Both orientations were refined separately to completion. Final residual errors at 2.25 A resolution for the 2358 reflections above 2 sigma in F are R = 0.165 for one orientation (LexA) with 37 water molecules and 0.164 for the inverted drug orientation (LexB) with 40 water molecules. This molecular disorder is probably attributable to a weakening of binding to the AATT site occasioned by the imidazole-for-pyrrole substitution.
已解析出一种双阳离子勒克西托菌素与序列为CGCGAATTCGCG的B - DNA双链体复合物的X射线晶体结构。勒克西托菌素与纺锤菌素相同，只是第一个甲基吡咯环被甲基咪唑取代，将=CH - 转变为=N - 。晶体与不存在药物时的DNA十二聚体晶体同晶型。尽管用=N - 取代=CH - 的目的是使药物分子上的该位点与G.C碱基对兼容，但药物两个阳离子端的静电吸引占主导，并且这种勒克西托菌素与亲本纺锤菌素一样结合到相同的中央AATT位点。但与纺锤菌素不同的是，这种勒克西托菌素在晶体中表现出首尾无序。两种取向都分别精修至完成。对于F中2σ以上的2358个反射，在2.25 Å分辨率下，一种取向（LexA）有37个水分子，最终残余误差R = 0.165，而药物反向取向（LexB）有40个水分子，最终残余误差为0.164。这种分子无序可能归因于咪唑取代吡咯导致与AATT位点的结合减弱。
