TYMP Human

Thymidine Phosphorylase is a dimeric protein composed of two identical subunits, each consisting of 440 amino acids . The enzyme has a unique S-shaped structure with a deep cavity that serves as the binding site for thymine, thymidine, and phosphate . The catalytic mechanism involves the binding of phosphate before thymidine, followed by the release of 2-deoxyribose-1-phosphate after the nitrogenous base .

TP is involved in several metabolic pathways, including purine and pyrimidine metabolism . It is particularly important in the context of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare metabolic disorder caused by mutations in the TYMP gene . MNGIE is characterized by severe gastrointestinal and neurological symptoms due to the accumulation of toxic metabolites .

The recombinant expression of human TP (HsTP) has been a focus of research due to its therapeutic potential . However, expressing HsTP in Escherichia coli (E. coli) has proven challenging due to poor expression levels and inefficient PEGylation, a chemical modification crucial for enhancing the enzyme’s stability and serum persistence . Researchers have employed various strategies to improve the recombinant expression and PEGylation efficiency of HsTP, including phylogenetic and structural analysis, as well as rational surface engineering .

The therapeutic potential of recombinant HsTP lies in its application for enzyme replacement therapy (ERT) in MNGIE patients . Unlike bacterial enzymes, which can elicit adverse immune responses, human recombinant enzymes are less likely to be recognized as foreign by the immune system . This makes HsTP a promising candidate for developing safer and more effective treatments for MNGIE and other related disorders .