Structural analysis of the ferric-binding protein KfuA from Klebsiella pneumoniae.

ABSTRACT

Iron acquisition is an essential process of cell physiology for biological systems. In Klebsiella pneumoniae, the siderophore and ferric-acquisition ABC (ATP-Binding-Cassette) transporter KfuABC is utilized for iron uptake. Initial recognition of the various ferric sources in periplasm and transportation across the cytoplasmic membrane is performed by the substrate-binding protein (SBP) KfuA. Here we report the 2.0 Å resolution crystal structure of KfuA from K. pneumoniae, which crystallizes in the space group P1211 with a single monomer in the asymmetric unit. A bound metal ion reveals the residues required for binding ferric ions. Binding analysis shows that ferric iron and the iron-mimicking gallium bind with high affinity to KfuA. Growth curves show that gallium inhibits growth of K. pneumoniae whereas ferric iron enhances it. This work suggests a mechanism whereby gallium effectively competes with ferric iron, disrupting iron-dependent biological functions via binding to KfuA and leading to heightened antimicrobial efficacy. Significantly, humans lack equivalent ABC transporters like SBP KfuA, underscoring the potential of KfuA as an attractive target for therapeutic intervention.