Kynureninase
kynureninase | |||||||||
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KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Ensembl | |||||||||
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RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 2: 142.88 – 143.06 Mb | Chr 2: 43.45 – 43.57 Mb | |||||||
PubMed search | [4] | [5] |
View/Edit Human | View/Edit Mouse |
Kynureninase or L-Kynurenine hydrolase (KYNU) (
KYNU is part of the pathway for the catabolism of Trp and the biosynthesis of NAD cofactors from tryptophan (Trp).
Kynureninase catalyzes the following reaction:
- L-kynurenine + H2O ↔ anthranilate + L-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.[1][8] 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.[1]
Function
In KYNU reaction, PLP facilitates Cβ-Cγ bond cleavage. The reaction follows the same steps as the transamination reaction but does not hydrolyze the tautomerized Schiff 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.
References
- ^ PMID 17300176.
- ^ a b c GRCh38: Ensembl release 89: ENSG00000115919 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026866 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8706755.
- S2CID 36265922.
- PMID 19143568.
Further reading
- Lima S, Khristoforov R, Momany C, Phillips RS (2007). "Crystal structure of Homo sapiens kynureninase". Biochemistry. 46 (10): 2735–2744. PMID 17300176.
- Heyes MP, Chen CY, Major EO, Saito K (1997). "Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types". Biochem. J. 326 (2): 351–6. PMID 9291104.
- Rose JE, Behm FM, Drgon T, et al. (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. PMID 20379614.
- 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. PMID 16080802.
- 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. PMID 6468727.
- Ubbink JB, Vermaak WJ, Bissbort SH (1991). "High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels". J. Chromatogr. 566 (2): 369–75. PMID 1939450.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Magni G, Amici A, Emanuelli M, et al. (2004). "Enzymology of NAD+ homeostasis in man". Cell. Mol. Life Sci. 61 (1): 19–34. S2CID 22041610.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- 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. S2CID 13295336.
- Walsh HA, Botting NP (2002). "Purification and biochemical characterization of some of the properties of recombinant human kynureninase". Eur. J. Biochem. 269 (8): 2069–74. PMID 11985583.
- 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. PMID 9373149.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Kynureninase