Pharmaceutical Institute, University of Bonn, 53119 Bonn, Germany.
Institute of Physical and Theoretical Chemistry, University of Bonn, 53115 Bonn, Germany.
Biochim Biophys Acta Gen Subj. 2017 Mar;1861(3):683-697. doi: 10.1016/j.bbagen.2016.12.021. Epub 2016 Dec 22.
Heme is an important nutritional iron source for almost all bacteria. Elevated heme concentrations, in contrast, are toxic e.g. due to the generation of reactive oxygen species. The cellular heme concentration thus requires tight regulation. The observation of heme acting as an effector molecule in heme-uptake and -utilization processes is rather new and many of these processes are unknown or rarely understood on the molecular level.
We describe processes involving transient heme-protein interaction in bacteria and highlight the regulatory function of heme at key steps during heme uptake and utilization. We furthermore focus on essential structural aspects of heme binding to respective proteins.
The structural and functional basis for heme-regulated processes in bacteria is diverse and ranges from increased degradation to extended half-life and from inhibition to activation of the respective heme-regulated protein. The large variety of effects is attributed to the versatile ability of heme to interact with proteins in different ways.
Knowledge of the molecular mechanism of transient heme-protein interaction is central to understand the heme-regulated processes in bacteria. The heme-binding proteins involved in these processes represent potential targets for the development of novel antibacterial drugs. New antibacterial strategies are urgently needed to combat antibiotic resistance.
血红素是几乎所有细菌的重要营养铁源。相比之下，升高的血红素浓度是有毒的，例如由于活性氧的产生。因此，细胞血红素浓度需要严格的调节。血红素作为血红素摄取和利用过程中的效应分子的作用是相当新的，许多这些过程在分子水平上是未知的或很少被理解。
我们描述了细菌中涉及瞬时血红素-蛋白质相互作用的过程，并强调了血红素在血红素摄取和利用过程中的关键步骤中的调节功能。我们还着重介绍了血红素与相应蛋白质结合的基本结构方面。
细菌中血红素调节过程的结构和功能基础多种多样，范围从增加降解到延长半衰期，从抑制到激活相应的血红素调节蛋白。大量的影响归因于血红素与蛋白质相互作用的多种方式。
了解瞬时血红素-蛋白质相互作用的分子机制是理解细菌中血红素调节过程的核心。参与这些过程的血红素结合蛋白代表了开发新型抗菌药物的潜在靶点。迫切需要新的抗菌策略来对抗抗生素耐药性。
