McGrath M, Cascio D, Williams R, Johnson D, Greene M, McPherson A
Department of Biochemistry, University of California, Riverside 92521.
Mol Pharmacol. 1987 Nov;32(5):600-5.
Propidium iodide, an antitumor compound, was diffused into crystals of a complex between RNase A and deoxytetraadenylate (dpA)4). This complex has four deoxyoligomers bound per protein molecule. A difference Fourier analysis at 2.9 A showed that the principal binding site for the propidium in the crystals was a hydrophobic depression on the side of RNase away from the active site and apparently involves methionine 13 and phenylalanine 8. Binding of propidium at this site produces small conformational changes that effect binding of nucleotides at the active site of the enzyme. Fluorescence titrations in the presence and absence of nucleotide inhibitors suggested that propidium iodide is a competitive inhibitor of the enzyme with a Kl of approximately 1 mM. No significant binding of propidium to the 16 nucleotides of single-stranded DNA associated with each protein molecule was observed.
碘化丙啶是一种抗肿瘤化合物，它扩散到核糖核酸酶A（RNase A）与脱氧四腺苷酸（dpA）4形成的复合物晶体中。该复合物每个蛋白质分子结合有四个脱氧寡聚物。在2.9埃分辨率下的差值傅里叶分析表明，晶体中碘化丙啶的主要结合位点是RNase远离活性位点一侧的一个疏水凹陷，显然涉及甲硫氨酸13和苯丙氨酸8。碘化丙啶在此位点的结合会产生微小的构象变化，影响酶活性位点处核苷酸的结合。在有和没有核苷酸抑制剂存在的情况下进行的荧光滴定表明，碘化丙啶是该酶的竞争性抑制剂，其解离常数（Kl）约为1 mM。未观察到碘化丙啶与每个蛋白质分子所结合的16个单链DNA核苷酸有明显结合。
