Quantifying structural relationships of metal-binding sites suggests origins of biological electron transfer

Computational exploration of similarities among metal-binding protein structural motifs elucidates the origins of life.

Activity of Phosvitin in Hydroxyapatite Acid-Damage Immersion and Antimicrobial Assays

Phosvitin, the most highly phosphorylated metal-binding protein found in nature, binds more than 100 calcium ions, and has been identified as an agent that could be used to generate biomineralization scaffolds. Because of published reports describing phosvitin’s affinity for calcium and potential antibiotic activity, this study was undertaken in order to evaluate phosvitin for both antibiotic activity against common microorganisms and the ability to protect hydroxyapatite surfaces from acid damage. To more clearly define its antibiotic action, the effects of phosvitin on Micrococcus luteus, P. mirabilis, B. cereus, E. coli, and S. epidermidis were evaluated. In both Kirby–Bauer tests and liquid culture growth inhibition assays, phosvitin inhibited M. luteus, a microorganism that thrives in the human mouth, but not the other bacteria tested. The MIC of phosvitin was determined to be 31.3 μg/mL when delivered in 1 mM CaCl2 but was 0.5 mg/mL in the absence of added calcium. Expanding on the potential impacts of phosvitin on the mouth, its action was evaluated in a model of tooth decay represented by acid-damaged hydroxyapatite discs. SEM, AFM, and FAAS analyses revealed that pretreatment of discs with phosvitin modulated the damage-induced morphology and topography changes associated with acid-damaged discs.

Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis

Although the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to developing ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in Trf-LKO mice significantly reduced hepatic iron accumulation, thereby reducing ferroptosis-mediated liver fibrosis induced by either a high-iron diet or CCl4 injections. Finally, we found that patients with liver cirrhosis have significantly lower levels of serum transferrin and hepatic transferrin, as well as higher levels of hepatic iron and lipid peroxidation, compared with healthy control subjects. Taken together, these data indicate that hepatic transferrin plays a protective role in maintaining liver function, providing a possible therapeutic target for preventing ferroptosis-induced liver fibrosis.