Müller J J, Lapko A, Bourenkov G, Ruckpaul K, Heinemann U
Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.
J Biol Chem. 2001 Jan 26;276(4):2786-9. doi: 10.1074/jbc.M008501200. Epub 2000 Oct 25.
The steroid hydroxylating system of adrenal cortex mitochondria consists of the membrane-attached NADPH-dependent adrenodoxin reductase (AR), the soluble one-electron transport protein adrenodoxin (Adx), and a membrane-integrated cytochrome P450 of the CYP11 family. In the 2.3-A resolution crystal structure of the Adx.AR complex, 580 A(2) of partly polar surface are buried. Main interaction sites are centered around Asp(79), Asp(76), Asp(72), and Asp(39) of Adx and around Arg(211), Arg(240), Arg(244), and Lys(27) of AR, respectively. In particular, the region around Asp(39) defines a new protein interaction site for Adx, similar to those found in plant and bacterial ferredoxins. Additional contacts involve the electron transfer region between the redox centers of AR and Adx and C-terminal residues of Adx. The Adx residues Asp(113) to Arg(115) adopt 3(10)-helical conformation and engage in loose intermolecular contacts within a deep cleft of AR. Complex formation is accompanied by a slight domain rearrangement in AR. The [2Fe-2S] cluster of Adx and the isoalloxazine rings of FAD of AR are 10 A apart suggesting a possible electron transfer route between these redox centers. The AR.Adx complex represents the first structure of a biologically relevant complex between a ferredoxin and its reductase.
肾上腺皮质线粒体的类固醇羟化系统由膜附着的NADPH依赖性肾上腺皮质铁氧还蛋白还原酶（AR）、可溶性单电子转运蛋白肾上腺皮质铁氧还蛋白（Adx）以及CYP11家族的膜整合细胞色素P450组成。在Adx.AR复合物的2.3埃分辨率晶体结构中，580埃²的部分极性表面被掩埋。主要相互作用位点分别以Adx的天冬氨酸（Asp）79、天冬氨酸76、天冬氨酸72和天冬氨酸39以及AR的精氨酸（Arg）211、精氨酸240、精氨酸244和赖氨酸（Lys）27为中心。特别是，天冬氨酸39周围的区域定义了Adx的一个新的蛋白质相互作用位点，类似于在植物和细菌铁氧还蛋白中发现的位点。额外的接触涉及AR和Adx的氧化还原中心之间的电子转移区域以及Adx的C末端残基。Adx残基天冬氨酸113至精氨酸115采用3(10)-螺旋构象，并在AR的一个深裂隙内进行松散的分子间接触。复合物的形成伴随着AR中轻微的结构域重排。Adx的[2Fe-2S]簇和AR的FAD的异咯嗪环相距10埃，表明这些氧化还原中心之间可能存在电子转移途径。AR.Adx复合物代表了铁氧还蛋白与其还原酶之间生物学相关复合物的首个结构。
