2-hydroxychromene-2-carboxylate isomerase (HCCA isomerase)

2-hydroxychromene-2-carboxylate isomerase (EC 5.99.1.4) is an enzyme that catalyzes the glutathione-dependent isomerization of 2-hydroxychromene-2-carboxylate into trans-o-hydroxybenzylidene pyruvate. Originally characterized in bacteria such as Pseudomonas putida for its role in the naphthalene catabolic pathway, its human ortholog is known as Glutathione S-transferase kappa 1 (GSTK1) or DsbA-like protein (DsbA-L). In humans, this enzyme is localized to the mitochondria and peroxisomes, where it plays a vital role in lipid metabolism and the multimerization of adiponectin, a hormone essential for insulin sensitivity. Due to its regulatory influence on adiponectin, the enzyme is considered a potential therapeutic target for treating metabolic disorders such as obesity, type 2 diabetes, and insulin resistance. While no clinical drugs currently target this isomerase, research into its structure and mechanism has identified small-molecule inhibitors like S-hexylglutathione, which serve as tools for further drug discovery. The enzyme's dual role in environmental bioremediation and human metabolic health makes it a subject of significant interest in both biotechnology and pharmacology.

Other names

2-hydroxychromene-2-carboxylic acid isomerase2HC2CA isomerase2-hydroxy-2H-chromene-2-carboxylate isomeraseGlutathione S-transferase kappa 1GSTK1DsbA-like proteinDsbA-LnahDdoxJ