Recombinant Human AGXT protein

Alanine-glyoxylate aminotransferase (AGXT) is a peroxisomal enzyme critical for glyoxylate metabolism in humans. It catalyzes the conversion of alanine and glyoxylate to pyruvate and glycine, thereby preventing the accumulation of glyoxylate, which can be oxidized to oxalate—a key contributor to kidney stone formation. AGXT deficiency due to genetic mutations causes primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder characterized by excessive oxalate production, leading to nephrocalcinosis, kidney failure, and systemic oxalosis. Over 200 AGXT variants have been identified, with some causing protein misfolding, mistargeting (e.g., mitochondrial mislocalization instead of peroxisomal retention), or reduced catalytic activity.

Recombinant AGXT proteins are engineered to study the enzyme’s structure-function relationships, mutation-induced dysfunction, and potential therapeutic strategies. These proteins are typically expressed in bacterial (e.g., *E. coli*) or mammalian systems to ensure proper folding and post-translational modifications, such as pyridoxal 5'-phosphate (PLP) cofactor binding. Studies using recombinant AGXT have elucidated mechanisms underlying PH1. including aggregation-prone mutations (e.g., Gly170Arg) and impaired dimerization. Furthermore, recombinant AGXT serves as a tool for drug discovery, enabling high-throughput screening of pharmacological chaperones (e.g., vitamin B6 derivatives) that stabilize mutant enzymes or enhance their activity. Recent advances include gene therapy and mRNA-based approaches to restore AGXT function in PH1 patients. The development of recombinant AGXT variants with improved stability or catalytic efficiency also holds promise for enzyme replacement therapies. Overall, recombinant AGXT models are indispensable for understanding disease pathology and advancing targeted treatments for hyperoxaluria.