Ancestral protein reconstruction reveals the mechanism of substrate specificity in FN3K-mediated deglycation.

ABSTRACT: Protein glycation is a detrimental byproduct of living cells' reliance on carbohydrate metabolism, and nearly all organisms encode kinases that facilitate the removal of early glycation products. In humans, these repair functions are performed by Fructosamine-3 kinase (FN3K) and Ketosamine-3 kinase (KT3K) enzymes which share conserved catalytic mechanisms but differ in substrate specificity. Recent structural studies defined key active site residues required for FN3K activity on a model substrate, yet the molecular basis for differential substrate recognition by FN3K and KT3K remains unresolved. Here, we integrate phylogenetic analysis, ancestral protein reconstruction (APR), and mutational biochemistry to to elucidate how substrate specificity evolved within the fructosamine-3 kinase fami

SUBMITTER: Matlack JK 

PROVIDER: S-EPMC12324494 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature