Biology:Kynureninase
| kynureninase | |||||||||
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 Crystal structure of Homo sapiens kynureninase.[1] | |||||||||
| Identifiers | |||||||||
| EC number | 3.7.1.3 | ||||||||
| CAS number | 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 | ||||||||
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 Generic protein structure example |
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.[2][3]
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][4] 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.
 The KYNU's reaction mechanism. The color scheme is as follows: KYNU, PLP, substrate names, inorganic molecules, 3hAn's moiety, Ala's moiety |
References
- ↑ 1.0 1.1 1.2 PDB: 2HZP; "Crystal structure of Homo sapiens kynureninase". Biochemistry 46 (10): 2735–44. March 2007. doi:10.1021/bi0616697. PMID 17300176.
- ↑ "Isolation and expression of a cDNA clone encoding human kynureninase". Eur. J. Biochem. 239 (2): 460–8. July 1996. doi:10.1111/j.1432-1033.1996.0460u.x. PMID 8706755.
- ↑ "Cloning and recombinant expression of rat and human kynureninase". FEBS Lett. 408 (1): 5–10. May 1997. doi:10.1016/S0014-5793(97)00374-8. PMID 9180257.
- ↑ PDB: 3E9K; "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. January 2009. doi:10.1021/jm8010806. PMID 19143568.
Further reading
- "Crystal structure of Homo sapiens kynureninase". Biochemistry 46 (10): 2735–2744. 2007. doi:10.1021/bi0616697. PMID 17300176.
- "Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types.". Biochem. J. 326 (2): 351–6. 1997. doi:10.1042/bj3260351. PMID 9291104.
- "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.". Mol. Med. 16 (7–8): 247–53. 2010. doi:10.2119/molmed.2009.00159. PMID 20379614.
- "[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. 2005. PMID 16080802.
- "Intracellular localization and characterization of 3-hydroxykynureninase in human liver.". Int. J. Biochem. 16 (6): 623–8. 1984. doi:10.1016/0020-711x(84)90031-4. PMID 6468727.
- "High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels.". J. Chromatogr. 566 (2): 369–75. 1991. doi:10.1016/0378-4347(91)80253-9. PMID 1939450.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Enzymology of NAD+ homeostasis in man.". Cell. Mol. Life Sci. 61 (1): 19–34. 2004. doi:10.1007/s00018-003-3161-1. PMID 14704851.
- "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. 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase.". J. Inherit. Metab. Dis. 30 (2): 248–55. 2007. doi:10.1007/s10545-007-0396-2. PMID 17334708.
- "Purification and biochemical characterization of some of the properties of recombinant human kynureninase.". Eur. J. Biochem. 269 (8): 2069–74. 2002. doi:10.1046/j.1432-1033.2002.02854.x. PMID 11985583.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1–2): 149–56. 1997. 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
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