Nonselenoproteins

Nonselenoproteins are proteins that contain selenium as a cofactor but do not incorporate the amino acid selenocysteine (Sec) into their structure. Unlike selenoproteins, which rely on Sec for catalytic or structural functions, nonselenoproteins bind selenium in alternative forms, such as selenocystine (a disulfide-linked dimer of Sec), selenophosphate, or as part of other selenium-containing moieties. This distinction is important because it highlights a broader role for selenium in protein function beyond the incorporation of Sec.

The discovery of nonselenoproteins emerged from studies on selenium metabolism and its diverse biochemical roles. One well-characterized example is the selenocystine-containing protein found in certain bacteria, such as *Escherichia coli*, where it functions in redox regulation. Another notable case involves selenophosphate synthetase, an enzyme that generates selenophosphate—a precursor for Sec biosynthesis—but does not itself contain Sec. These proteins often participate in redox reactions, detoxification processes, or metabolic pathways where selenium’s chemical properties, such as its ability to cycle between oxidation states, are exploited.

The identification of nonselenoproteins has expanded the understanding of selenium’s biological significance. While selenoproteins are well-studied for their roles in antioxidant defense (e.g., glutathione peroxidase) and thyroid hormone metabolism, nonselenoproteins contribute to selenium’s broader physiological functions, including microbial survival, stress responses, and metabolic regulation. Research into these proteins remains active, particularly in microbial systems, where selenium’s role in nonselenoprotein contexts is more pronounced than in eukaryotes.

The study of nonselenoproteins also raises questions about the evolutionary and functional diversity of selenium utilization. Some organisms may rely more heavily on nonselenoprotein pathways under conditions of selenium limitation or specific environmental pressures. Further investigation into these proteins could provide insights into novel therapeutic targets or biochemical mechanisms where selenium plays an unexpected yet critical role.