Kynureninase (KYNU) (KYNU)

Human kynureninase (KYNU) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that plays a central role in the kynurenine pathway, the primary route for tryptophan metabolism in humans (UniProt Q16719). It catalyzes the hydrolytic cleavage of L-kynurenine and 3-hydroxy-L-kynurenine into anthranilic acid and 3-hydroxyanthranilic acid, respectively, which are essential precursors for the biosynthesis of NAD+ (PubMed: 16140358). A notable structural feature of human kynureninase is the presence of an ELDKWA motif within its H4 helix, which is identical to a highly conserved neutralizing epitope on the HIV-1 gp41 envelope protein (PubMed: 15105495). This molecular mimicry causes the broadly neutralizing HIV antibody 2F5 to cross-react with human kynureninase, a factor believed to contribute to the immunological tolerance that prevents the induction of 2F5-like antibodies by HIV vaccines (PubMed: 16140358). In oncology, kynureninase is a therapeutic target because the accumulation of kynurenine in the tumor microenvironment suppresses T-cell activity via the aryl hydrocarbon receptor (AhR) (PubMed: 28114274). Engineered versions of the enzyme, such as PEGylated kynureninase, are being developed to deplete kynurenine levels and enhance the efficacy of cancer immunotherapies (PubMed: 28114274).

Other names

L-kynurenine hydrolaseKYNUKynurenine hydrolaseL-Kynurenine hydrolase

Kynureninase catalyzes the hydrolytic cleavage of L-kynurenine or 3-hydroxy-L-kynurenine into anthranilic acid or 3-hydroxyanthranilic acid and L-alanine. In therapeutic applications, PEGylated kynureninase is used to enzymatically deplete kynurenine from the tumor microenvironment, thereby reversing kynurenine-mediated immunosuppression and activating anti-tumor T-cell responses.