Hans Henning Brewitz1, Gregor Hagelueken2, Diana Imhof3. 1. Pharmaceutical Institute, University of Bonn, 53119 Bonn, Germany. 2. Institute of Physical and Theoretical Chemistry, University of Bonn, 53115 Bonn, Germany. 3. Pharmaceutical Institute, University of Bonn, 53119 Bonn, Germany. Electronic address: dimhof@uni-bonn.de.
Abstract
BACKGROUND: 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. SCOPE OF REVIEW: 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. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
BACKGROUND: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. SCOPE OF REVIEW: 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. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
Authors: Eric A Johnson; Miranda M Russo; Dillon B Nye; Jamie L Schlessman; Juliette T J Lecomte Journal: Biochim Biophys Acta Gen Subj Date: 2018-08-10 Impact factor: 3.770
Authors: Jin-Long Gao; Ann H Kwan; Anthony Yammine; Xiaoyan Zhou; Jill Trewhella; Barbara M Hugrass; Daniel A T Collins; James Horne; Ping Ye; Derek Harty; Ky-Anh Nguyen; David A Gell; Neil Hunter Journal: Nat Commun Date: 2018-10-05 Impact factor: 14.919