title: Structure and functional analysis of the siderophore periplasmic binding protein from the fuscachelin gene cluster of Thermobifida fusca.
abstract: Iron acquisition is a complex, multicomponent process critical for most organisms' survival and virulence. Small iron chelating molecules, siderophores, mediate transport as key components of common pathways for iron assimilation in many microorganisms. The chemistry and biology of the extraordinary tight and specific metal binding siderophores is of general interest in terms of host/guest chemistry and is a potential target toward the development of therapeutic treatments for microbial virulence. The siderophore pathway of the moderate thermophile, Thermobifida fusca, is an excellent model system to study the process in Gram-positive bacteria. Here we describe the structure and characterization of the siderophore periplasmic binding protein, FscJ from the fuscachelin gene cluster of T. fusca. The structure shows a di-domain arrangement connected with a long α-helix hinge. Several X-ray structures detail ligand-free conformational changes at different pH values, illustrating complex interdomain flexibility of the siderophore receptors. We demonstrated that FscJ has a unique recognition mechanism and details the binding interaction with ferric-fuscachelin A through ITC and docking analysis. The presented work provides a structural basis for the complex molecular mechanisms of siderophore recognition and transportation.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, Florida, 32611.
authors.forename: Kunhua
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, Florida, 32611.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bruner
mesh_terms: D039903:Actinobacteria / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D033902:Periplasmic Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D017262:Siderophores / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D033902:Periplasmic Binding Proteins; D017262:Siderophores
keywords: crystal structure; iron acquisition; protein dynamics; siderophore; substrate binding protein