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.
In KYNU reaction, PLP facilitates Cβ-Cγ bond cleavage. The reaction follows the same steps as the transamination reaction but does not hydrolyze the tautomerizedSchiff base. The proposed reaction mechanism involves an attack of an enzyme 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.
The KYNU's reaction mechanism.
The color scheme is as follows: KYNU, PLP, substrate names, inorganic molecules, 3hAn's moiety, Ala's moiety
^Alberati-Giani D, Buchli R, Malherbe P, Broger C, Lang G, Köhler C, Lahm HW, Cesura AM (July 1996). "Isolation and expression of a cDNA clone encoding human kynureninase". Eur. J. Biochem. 239 (2): 460–8. doi:10.1111/j.1432-1033.1996.0460u.x. PMID8706755.
^Toma S, Nakamura M, Toné S, Okuno E, Kido R, Breton J, Avanzi N, Cozzi L, Speciale C, Mostardini M, Gatti S, Benatti L (May 1997). "Cloning and recombinant expression of rat and human kynureninase". FEBS Lett. 408 (1): 5–10. doi:10.1016/S0014-5793(97)00374-8. PMID9180257.
^PDB: 3E9K; Lima S, Kumar S, Gawandi V, Momany C, Phillips RS (January 2009). "Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity". J. Med. Chem. 52 (2): 389–96. doi:10.1021/jm8010806. PMID19143568.
Zhang Y, Zhang KX, He X, et al. (2005). "[A polymorphism of kynureninase gene in a hypertensive candidate chromosomal region is associated with essential hypertension]". Zhonghua Xin Xue Guan Bing Za Zhi. 33 (7): 588–91. PMID16080802.
Inada J, Okuno E, Kimura M, Kido R (1984). "Intracellular localization and characterization of 3-hydroxykynureninase in human liver.". Int. J. Biochem. 16 (6): 623–8. doi:10.1016/0020-711x(84)90031-4. PMID6468727.
Ubbink JB, Vermaak WJ, Bissbort SH (1991). "High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels.". J. Chromatogr. 566 (2): 369–75. doi:10.1016/0378-4347(91)80253-9. PMID1939450.
Christensen M, Duno M, Lund AM, et al. (2007). "Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase.". J. Inherit. Metab. Dis. 30 (2): 248–55. doi:10.1007/s10545-007-0396-2. PMID17334708.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.