Schumacher M A, Miller M C, Grkovic S, Brown M H, Skurray R A, Brennan R G
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97201, USA.
Science. 2001 Dec 7;294(5549):2158-63. doi: 10.1126/science.1066020.
The Staphylococcus aureus multidrug binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by structurally diverse cationic lipophilic drugs. Here, we report the crystal structures of six QacR-drug complexes. Compared to the DNA bound structure, drug binding elicits a coil-to-helix transition that causes induction and creates an expansive multidrug-binding pocket, containing four glutamates and multiple aromatic and polar residues. These structures indicate the presence of separate but linked drug-binding sites within a single protein. This multisite drug-binding mechanism is consonant with studies on multidrug resistance transporters.
金黄色葡萄球菌多药结合蛋白QacR抑制多药转运蛋白基因qacA的转录，并由结构多样的阳离子亲脂性药物诱导。在此，我们报道了六种QacR-药物复合物的晶体结构。与DNA结合结构相比，药物结合引发了从卷曲到螺旋的转变，导致诱导并形成一个扩张的多药结合口袋，其中包含四个谷氨酸以及多个芳香族和极性残基。这些结构表明在单个蛋白质内存在独立但相连的药物结合位点。这种多位点药物结合机制与多药耐药转运蛋白的研究结果一致。
