Kynureninase

kynureninase
Crystal structure of Homo sapiens kynureninase.
Identifiers
EC no.	3.7.1.3
CAS no.	9024-78-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

KYNU
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2HZP, 3E9K
Identifiers
Aliases	KYNU, KYNUU, kynureninase, VCRL2
External IDs	OMIM: 605197; MGI: 1918039; HomoloGene: 2925; GeneCards: KYNU; OMA:KYNU - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q22.2 Start 142,877,657 bp End 143,055,833 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2|2 B Start 43,445,341 bp End 43,572,727 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva sperm epithelium of nasopharynx monocyte liver nasal epithelium right lobe of liver kidney tubule mucosa of urinary bladder granulocyte Top expressed in left lobe of liver yolk sac embryo epithelium of lens spleen embryo zygote right kidney blood mesenteric lymph nodes More reference expression data BioGPS n/a
Gene ontology Molecular function protein homodimerization activity kynureninase activity catalytic activity pyridoxal phosphate binding hydrolase activity 3-hydroxykynureninase activity Cellular component cytosol mitochondrion cytoplasm nucleoplasm Biological process pyridine nucleotide biosynthetic process response to vitamin B6 response to interferon-gamma tryptophan catabolic process to acetyl-CoA L-kynurenine catabolic process tryptophan catabolic process tryptophan catabolic process to kynurenine quinolinate biosynthetic process anthranilate metabolic process NAD biosynthetic process 'de novo' NAD biosynthetic process from tryptophan ageing Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8942 70789 Ensembl ENSG00000115919 ENSMUSG00000026866 UniProt Q16719 Q9CXF0 RefSeq (mRNA) NM_001032998 NM_001199241 NM_003937 NM_027552 NM_001289593 NM_001289594 NM_001398676 RefSeq (protein) NP_001028170 NP_001186170 NP_003928 NP_001276522 NP_001276523 NP_081828 NP_001385605 Location (UCSC) Chr 2: 142.88 – 143.06 Mb Chr 2: 43.45 – 43.57 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Kynureninase or L-Kynurenine hydrolase (KYNU) (EC 3.7.1.3) is a PLP dependent enzyme that catalyses the cleavage of kynurenine (Kyn) into anthranilic acid (Ant). It can also act on 3-hydroxykynurenine (to produce 3-hydroxyanthranilate) and some other (3-arylcarbonyl)-alanines. Humans express one kynureninase enzyme that is encoded by the KYNU gene located on chromosome 2.

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. 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 C_β-C_γ 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 (C_γ) of the tautomerized 3hKyn-PLP Schiff base. This is followed by C_β-C_γ 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.   KYNU   PLP   substrate names   inorganic molecules   3hAn's moiety   Ala's moiety

Further reading

• Lima S, Khristoforov R, Momany C, Phillips RS (2007). "Crystal structure of Homo sapiens kynureninase". Biochemistry. 46 (10): 2735–2744. doi:10.1021/bi0616697. PMC 2531291. 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. doi:10.1042/bj3260351. PMC 1218677. 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. doi:10.2119/molmed.2009.00159. PMC 2896464. 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. doi:10.1016/0020-711x(84)90031-4. 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. doi:10.1016/0378-4347(91)80253-9. 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. doi:10.1016/0378-1119(94)90802-8. 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. doi:10.1007/s00018-003-3161-1. PMC 11138864. PMID 14704851. 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. 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. doi:10.1007/s10545-007-0396-2. PMID 17334708. 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. doi:10.1046/j.1432-1033.2002.02854.x. 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. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Kynureninase