The human thioredoxin-1 enzyme is a target-selective disulfide reductase / anti-oxidant protein that is found both intracellularly as well as secreted. Thioredoxin is highly selective for only certain disulfide bonds due to its shaped active site structure, and in contrast to non-selective small molecule reducing agents it has an unusually acidic pKa (pH 6.2) as a result of conserved hydrogen bonding to its catalytic Cys. These unique features serve to stabilize activity across a broad physiological pH range and allow thioredoxin to selectively modulate the activity or structural properties of its disulfide-protein targets which include enzymes, transcription factors, secreted antimicrobial peptides, and epithelial mucus proteins.
Thioredoxin is known to be an essential human protein with distinct intracellular and extracellular functions. Cytosolic thioredoxin is necessary for cell growth and influences multiple essential cellular processes from nucleotide biosynthesis and programmed cell death (apoptosis) to modulation of the important regulatory transcription factors NfKb and ASK-1. In contrast, secreted thioredoxin appears to play a largely homeostatic role, with published studies demonstrating anti-inflammatory, anti-infective, and mucus viscosity-normalizing properties.
Work from the laboratory of Dr. Carl White (Professor of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; previously Professor of Pediatrics at National Jewish Medical and Research Center, now National Jewish Health) has shown that thioredoxin-targeted disulfide bonds are present in the cysteine-rich soluble mucin proteins on the airway surface and that thioredoxin is capable of reducing these bonds with high potency.