Periplasmic Binding Proteins Involved in Bacterial Iron Uptake

Abstract

This chapter focuses on the structural biology of periplasmic binding proteins (PBPs) in general and, more specifically, on the iron binding PBPs whose structures have been solved: ferric ion binding proteins (FbpA), siderophore-binding protein (FhuD), and vitamin B12 binding protein (BtuF). It also discusses some studies of the TroA protein, which is structurally related to FhuD. Although not involved in iron transport or iron transport-related events, maltose binding protein (MBP) is one of the best-characterized PBPs and is therefore a good mechanistic model of periplasmic transport. A portion of the chapter describes different experimental techniques which have been used to characterize the motions that MBP undergoes on ligand association or dissociation. Although the binding pocket of FhuA is deeper than that of FhuD, it still could accommodate a more bulky ligand such as albomycin. Albomycin consists of an antibiotic group attached to a hydroxamate siderophore via an amino acyl linker. Although rational design of a novel, efficient antibiotic by chemical conjugation is challenging, the Trojan horse design may become increasingly important due to the growing problem of antibiotic resistance.