Crystal structure of the iron-dependent regulator (IdeR) from Mycobacterium tuberculosis shows both metal binding sites fully occupied.-猫眼课题宝

结核分枝杆菌铁依赖性调节因子 (IdeR) 的晶体结构显示两个金属结合位点均被完全占据。

DOI：

10.1006/jmbi.1998.2339

发表时间：

1999

期刊：

Journal of molecular biology.

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Pohl,E;Holmes,RK;Hol,WG

铁依赖性调节因子是在几种革兰氏阳性细菌中发现的金属活化的DNA结合蛋白家族。这些蛋白质是毒力因子和细菌铁吸收系统蛋白质的负调节剂。在这项研究中，我们提出的晶体结构的铁依赖性调节（IdeR）从结核分枝杆菌，结核病的病原体。该蛋白质属于六方晶系P62空间群，晶胞参数a=B= 92.6nm，c = 63.2nm。目前的模型包括N-末端DNA结合结构域（残基1-73）和二聚化结构域（残基74-140），而第三个结构域（残基141-230）太无序而不能包括在内。该分子位于产生功能性二聚体的晶体学2-折叠轴上。单体的整体结构与白喉棒状杆菌的白喉毒素阻遏物（DtxR）同源调节子具有许多特征。然而，这里报道的与锌复合的IdeR结构是第一个两个金属结合位点都被完全占据的野生型阻遏物结构。该晶体结构表明Met 10和Cys 102的最可能的Sγ都是第二金属结合位点的配体。此外，在apo-DtxR和holo-IdeR之间的三级结构中有重要的变化，使推定的DNA结合螺旋在holo阻遏物中更靠近在一起。金属结合可能导致载脂蛋白和全野生型阻遏物之间的这些结构变化的机制进行了讨论。

Iron-dependent regulators are a family of metal-activated DNA binding proteins found in several Gram-positive bacteria. These proteins are negative regulators of virulence factors and of proteins of bacterial iron-uptake systems. In this study we present the crystal structure of the iron-dependent regulator (IdeR) fromMycobacteriumtuberculosis , the causative agent of tuberculosis. The protein crystallizes in the hexagonal space group P 62with unit cell dimensions a=b=92.6Å,c =63.2Å. The current model comprises the N-terminal DNA-binding domain (residues 1-73) and the dimerization domain (residues 74-140), while the third domain (residues 141-230) is too disordered to be included. The molecule lies on a crystallographic 2-fold axis that generates the functional dimer. The overall structure of the monomer shares many features with the homologous regulator, diphtheria toxin repressor (DtxR) from Corynebacteriumdiphtheriae. The IdeR structure in complex with Zinc reported here is, however, the first wild-type repressor structure with both metal binding sites fully occupied. This crystal structure reveals that both Met10 and most probably the Sγof Cys102 are ligands of the second metal binding site. In addition, there are important changes in the tertiary structure between apo-DtxR and holo-IdeR bringing the putative DNA binding helices closer together in the holo repressor. The mechanism by which metal binding may cause these structural changes between apo and holo wild-type repressor is discussed.