Transferrin and Metalloantibiotics

We study the metal binding properties of iron transport proteins, such as human transferrin and the bacterial equivalent, ferric-ion-binding protein (Fbp). We have shown that these proteins can accommodate oxo-metal clusters, i.e. small mineral fragments. The proteins prove to be versatile metal-binding scaffolds, as multinuclear oxo-metal clusters of zirconium, hafnium and titanium can be accommodated. These studies provide a model for protein-mediated mineralization.

Efficient iron acquisition is required for the virulence of pathogenic bacteria. Metal compounds that inhibit this iron uptake mechanism carry medicinal potential. The tight binding of Ti(IV) to Fbp, for instance, has promising characteristics ffor consideration as a candidate metalloantibiotic. We recently discovered that transferrin readily forms worm-like fibrils and in so doing gives rise to periodic iron nanomineralization in the fibrils. This process might be related to how iron is deposited in the brain, a process thought to be related to some forms of neurodegerative diseases.

A novel protein-mineral interface: a hafnium cluster bound to Fbp