D86H

Deciphering and Improving Human Homogentisate 1,2-Dioxygenase Function Through Knowledge Gaining Directed Evolution: Implications for Alkaptonuria

Human homogentisate 1,2-dioxygenase (HGD) catalyses the oxidative cleavage of homogentisic acid (HGA) to maleylacetoacetate (MAA), a key step in tyrosine degradation. Loss of HGD activity causes alkaptonuria (AKU), a rare inherited metabolic disorder characterized by toxic HGA accumulation. Current therapy with nitisinone lowers HGA levels but does not restore HGD function, motivating further investigation of HGD structure-function relationships.