Lucarelli Debora, Russo Santina, Garman Elspeth, Milano Anna, Meyer-Klaucke Wolfram, Pohl Ehmke
European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany.
Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen, Switzerland.
J Biol Chem. 2007 Mar 30;282(13):9914-9922. doi: 10.1074/jbc.M609974200. Epub 2007 Jan 9.
Members of the ferric/zinc uptake regulator (Fur/Zur) family are the central metal-dependent regulator proteins in many Gram-negative and -positive bacteria. They are responsible for the control of a wide variety of basic physiological processes and the expression of important virulence factors in human pathogens. Therefore, Fur has gathered significant interest as a potential target for novel antibiotics. Here we report the crystal structure of FurB from Mycobacterium tuberculosis at a resolution of 2.7A, and we present biochemical and spectroscopic data that allow us to propose the functional role of this protein. Although the overall fold of FurB with an N-terminal DNA binding domain and a C-terminal dimerization domain is conserved among the Zur/Fur family, large differences in the spatial arrangement of the two domains with respect to each other can be observed. The biochemical and spectroscopic analysis presented here reveals that M. tuberculosis FurB is Zn(II)-dependent and is likely to control genes involved in the bacterial zinc uptake. The combination of the structural, spectroscopic, and biochemical results enables us to determine the structural basis for functional differences in this important family of bacterial regulators.
铁/锌摄取调节因子（Fur/Zur）家族成员是许多革兰氏阴性和阳性细菌中的核心金属依赖性调节蛋白。它们负责控制多种基本生理过程以及人类病原体中重要毒力因子的表达。因此，Fur作为新型抗生素的潜在靶点已引起了广泛关注。在此，我们报道了结核分枝杆菌FurB的晶体结构，分辨率为2.7埃，并展示了生化和光谱数据，这些数据使我们能够提出该蛋白的功能作用。尽管FurB具有N端DNA结合结构域和C端二聚化结构域的整体折叠在Zur/Fur家族中是保守的，但可以观察到这两个结构域相对于彼此的空间排列存在很大差异。此处呈现的生化和光谱分析表明，结核分枝杆菌FurB是锌（II）依赖性的，可能控制参与细菌锌摄取的基因。结构、光谱和生化结果的结合使我们能够确定这个重要细菌调节因子家族功能差异的结构基础。
