Kynureninase

Kynureninase or L-Kynurenine hydrolase (KYNU) is a PLP dependent is_associated_with::enzyme that catalyses the cleavage of is_associated_with::kynurenine (Kyn) into is_associated_with::anthranilic acid (Ant). It can also act on 3hKyn (to produce is_associated_with::3hAnt) and some other (3-arylcarbonyl)-is_associated_with::alanines. Humans express one kynureninase enzyme that is encoded by the KYNU is_associated_with::gene located on chromosome 2.

KYNU is part of the pathway for the is_associated_with::catabolism of Trp and the biosynthesis of NAD cofactors from is_associated_with::tryptophan (Trp).

Kynureninase catalyzes the following reaction:


 * L-is_associated_with::kynurenine + H2O = anthranilate + L-is_associated_with::alanine

Structure
Kynureninase belongs to the class V group of aspartate aminotransferase superfamily of structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes. To date, two structures of human kynureninase have determined by X-ray diffraction with resolutions of 2.0 and 1.7 Å. Forty percent of the amino acids are arranged in an alpha helical and twelve percent are arranged in beta sheets. Docking of the kynurenine substrate into the active site suggests that Asn-333 and His-102 are involved in substrate binding.

Function
In KYNU reaction, PLP facilitates Cβ-Cγ bond cleavage. The reaction follows the same steps as the is_associated_with::transamination reaction but does not hydrolyze the is_associated_with::tautomerized is_associated_with::Schiff base. The proposed reaction mechanism involves an attack of an enzyme is_associated_with::nucleophile on the carbonyl carbon (Cγ) of the tautomerized 3hKyn-PLP Schiff base. This is followed by Cβ-Cγ bond cleavage to generate an acyl-enzyme intermediate together with a tautomerized Ala-PLP adduct. Hydrolysis of the acyl-enzyme then yields 3hAnt.