Panin L E, Kunitsyn V G, Tuzikov F V
State Institute of Biochemistry SD RAMS, Timakov Str. 2, Novosibirsk 630117, Russia.
J Phys Chem B. 2006 Jul 13;110(27):13560-71. doi: 10.1021/jp068011n.
A small-angle X-ray scattering study showed that the action of tetrahydrocortisol (THC) in complex with apolipoprotein A I (ApoA-I) on DNA leads to local melting of DNA. The most probable site of interaction between this complex and DNA is the (GCC)n-type sequence. Oligonucleotides (duplexes) of this type have been synthesized. It was demonstrated that the interaction of this oligonucleotide with the THC-ApoA-I complex leads to dissociation into complementary oligonucleotides. The latter ones also interact with the THC-ApoA-I complex. The kinetics of this multistep process is presented. The mechanism of interaction between hormones or their ApoA-I complexes and duplex CC(GCC)5.GG(CGG)5Li2 was studied using IR spectroscopy. It was shown that the interaction with THC or the THC-ApoA-I complex leads to the formation of hydrogen bonds between the OH group of the hormone A-ring and the C=O group of cytosine or guanine. Interaction with cortisol or the cortisol-ApoA-I complex leads to the formation of a hydrogen bond with the NH group of cytosine; in addition, THC and cortisol form hydrogen bonds with the PO2 group of the duplex and with the OH group of the monosaccharide. The interaction of ApoA-I with the duplex is accompanied by the formation of hydrogen bonds between the protein NH2 group and the C=O group of cytosine and the P=O group. The order-to-order structural transition takes place in the duplex under the action of THC or cortisol, with THC causing a higher ordering as compared to cortisol. The order-to-disorder structural transition occurs in the duplex under the action of the THC-ApoA-I, cortisol-ApoA-I, or ApoA-I complexes. Shifting the pH of the medium from 7.2 to 6.0 also leads to an order-to-disorder-type structural transition.
小角X射线散射研究表明，四氢皮质醇（THC）与载脂蛋白A I（ApoA-I）形成的复合物作用于DNA会导致DNA局部解链。该复合物与DNA之间最可能的相互作用位点是（GCC）n型序列。已合成了此类寡核苷酸（双链体）。结果表明，这种寡核苷酸与THC-ApoA-I复合物的相互作用会导致其解离为互补寡核苷酸。后者也会与THC-ApoA-I复合物相互作用。给出了这一多步过程的动力学。利用红外光谱研究了激素或其ApoA-I复合物与双链体CC（GCC）5.GG（CGG）5Li2之间的相互作用机制。结果表明，与THC或THC-ApoA-I复合物的相互作用会导致激素A环的OH基团与胞嘧啶或鸟嘌呤的C=O基团之间形成氢键。与皮质醇或皮质醇-ApoA-I复合物的相互作用会导致与胞嘧啶的NH基团形成氢键；此外，THC和皮质醇还会与双链体的PO2基团以及单糖的OH基团形成氢键。ApoA-I与双链体的相互作用伴随着蛋白质NH2基团与胞嘧啶的C=O基团以及P=O基团之间形成氢键。在THC或皮质醇的作用下，双链体会发生从有序到有序的结构转变，与皮质醇相比，THC会导致更高程度的有序化。在THC-ApoA-I、皮质醇-ApoA-I或ApoA-I复合物的作用下，双链体会发生从有序到无序的结构转变。将介质的pH从7.2调节到6.0也会导致从有序到无序型的结构转变。
