Jorge Fernandez-Perez, Akinobu Senoo, Jose M.M. Caaveiro, Makoto Nakakido, Susana de Vega, Ichiro Nakagawa, Kouhei Tsumoto
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引用次数: 0
Abstract
Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient.
期刊介绍:
Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome.
In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.