View source for Kynureninase

{{infobox enzyme
| Name       = kynureninase
| EC_number  = 3.7.1.3
| CAS_number = 9024-78-6
| GO_code    = 0030429
| image      = Kynureninase2HZP.jpg
| width      =
| caption    = Crystal structure of ''Homo sapiens'' kynureninase.<ref name="pmid17300176">{{PDB|2HZP}}; {{cite journal |vauthors=Lima S, Khristoforov R, Momany C, Phillips RS | title = Crystal structure of Homo sapiens kynureninase | journal = Biochemistry | volume = 46 | issue = 10 | pages = 2735–44 |date=March 2007 | pmid = 17300176 | pmc = 2531291 | doi = 10.1021/bi0616697 }}</ref> 
}}
{{Infobox_gene}}

'''Kynureninase''' or '''<small>L</small>-Kynurenine hydrolase''' (KYNU) ({{EC number|3.7.1.3}}) is a [[Pyridoxal-phosphate|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)-[[alanine]]s. Humans express one kynureninase enzyme that is encoded by the ''KYNU'' [[gene]] located on chromosome 2.<ref name="pmid8706755">{{cite journal |vauthors=Alberati-Giani D, Buchli R, Malherbe P, Broger C, Lang G, Köhler C, Lahm HW, Cesura AM | title = Isolation and expression of a cDNA clone encoding human kynureninase | journal = Eur. J. Biochem. | volume = 239 | issue = 2 | pages = 460–8 |date=July 1996 | pmid = 8706755 | doi = 10.1111/j.1432-1033.1996.0460u.x| doi-access = free }}</ref><ref name="pmid9180257">{{cite journal | vauthors = Toma S, Nakamura M, Toné S, Okuno E, Kido R, Breton J, Avanzi N, Cozzi L, Speciale C, Mostardini M, Gatti S, Benatti L | title = Cloning and recombinant expression of rat and human kynureninase | journal = FEBS Lett. | volume = 408 | issue = 1 | pages = 5–10 |date=May 1997 | pmid = 9180257 | doi = 10.1016/S0014-5793(97)00374-8| s2cid = 36265922 | doi-access = free }}</ref>

KYNU is part of the pathway for the [[catabolism]] of [[tryptophan|Trp]] and the biosynthesis of [[Nicotinamide adenine dinucleotide|NAD]] [[cofactor (biochemistry)|cofactor]]s from [[tryptophan]] (Trp).

Kynureninase catalyzes the following reaction:
:  <small>L</small>-[[kynurenine]] + H<sub>2</sub>O ↔ [[anthranilic acid|anthranilate]] + <small>L</small>-[[alanine]]

==Structure==
Kynureninase belongs to the [[aminotransferase, class V|class V]] group of [[aspartate transaminase|aspartate aminotransferase]] superfamily of structurally homologous pyridoxal 5'-phosphate ([[pyridoxal 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.<ref name="pmid17300176"/><ref name="pmid19143568">{{PDB|3E9K}}; {{cite journal |vauthors=Lima S, Kumar S, Gawandi V, Momany C, Phillips RS | title = Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity | journal = J. Med. Chem. | volume = 52 | issue = 2 | pages = 389–96 |date=January 2009 | pmid = 19143568 | doi = 10.1021/jm8010806 }}</ref> 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.<ref name="pmid17300176"/>

==Function==
In KYNU reaction, PLP facilitates C<sub>β</sub>-C<sub>γ</sub> bond cleavage. The reaction follows the same steps as the [[transamination]] reaction but does not hydrolyze the [[tautomer]]ized [[Schiff base]]. The proposed reaction mechanism involves an attack of an enzyme [[nucleophile]] on the carbonyl carbon (C<sub>γ</sub>) of the tautomerized 3hKyn-PLP Schiff base. This is followed by C<sub>β</sub>-C<sub>γ</sub> bond cleavage to generate an acyl-enzyme intermediate together with a tautomerized Ala-PLP adduct. Hydrolysis of the acyl-enzyme then yields 3hAnt.

{|
|[[File:Kynureninase reaction.png|frame|'''The KYNU's reaction mechanism'''. 
{{legend|blue|KYNU}}
{{legend|rgb(219,155,36)|PLP}}
{{legend|rgb(151,149,45)|substrate names}}
{{legend|rgb(128,0,0)|inorganic molecules}}
{{legend|red|3hAn's moiety}}
{{legend|rgb(230,192,230)|Ala's moiety}}]]
|}

==References==
{{reflist}}
{{Clear}}

==Further reading==
{{refbegin | 2}}
* {{cite journal|vauthors=Lima S, Khristoforov R, Momany C, Phillips RS | title=Crystal structure of Homo sapiens kynureninase| journal=Biochemistry| year=2007|volume=46| issue=10|pages=2735–2744|pmid=17300176| doi= 10.1021/bi0616697| pmc=2531291}}
*{{cite journal  |vauthors=Heyes MP, Chen CY, Major EO, Saito K |title=Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types. |journal=Biochem. J. |volume=326 |issue=  2|pages= 351–6 |year= 1997 |pmid= 9291104 |doi= 10.1042/bj3260351|pmc=1218677}}
*{{cite journal   |vauthors=Rose JE, Behm FM, Drgon T, etal |title=Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. |journal=Mol. Med. |volume=16 |issue= 7–8 |pages= 247–53 |pmid= 20379614 |doi= 10.2119/molmed.2009.00159 |pmc=2896464|year=2010 }}
*{{cite journal   |vauthors=Zhang Y, Zhang KX, He X, etal |title=[A polymorphism of kynureninase gene in a hypertensive candidate chromosomal region is associated with essential hypertension] |journal=Zhonghua Xin Xue Guan Bing Za Zhi |volume=33 |issue= 7 |pages= 588–91 |year= 2005 |pmid= 16080802 }}
*{{cite journal  |vauthors=Inada J, Okuno E, Kimura M, Kido R |title=Intracellular localization and characterization of 3-hydroxykynureninase in human liver. |journal=Int. J. Biochem. |volume=16 |issue= 6 |pages= 623–8 |year= 1984 |pmid= 6468727 |doi=  10.1016/0020-711x(84)90031-4}}
*{{cite journal  |vauthors=Ubbink JB, Vermaak WJ, Bissbort SH |title=High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels. |journal=J. Chromatogr. |volume=566 |issue= 2 |pages= 369–75 |year= 1991 |pmid= 1939450 |doi=  10.1016/0378-4347(91)80253-9}}
*{{cite journal  |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=  10.1016/0378-1119(94)90802-8}}
*{{cite journal   |vauthors=Magni G, Amici A, Emanuelli M, etal |title=Enzymology of NAD+ homeostasis in man. |journal=Cell. Mol. Life Sci. |volume=61 |issue= 1 |pages= 19–34 |year= 2004 |pmid= 14704851 |doi= 10.1007/s00018-003-3161-1 |s2cid=22041610 |pmc=11138864 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2002 |pmid= 12477932 |doi= 10.1073/pnas.242603899 |pmc=139241|bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal   |vauthors=Christensen M, Duno M, Lund AM, etal |title=Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase. |journal=J. Inherit. Metab. Dis. |volume=30 |issue= 2 |pages= 248–55 |year= 2007 |pmid= 17334708 |doi= 10.1007/s10545-007-0396-2 |s2cid=13295336 }}
*{{cite journal  |vauthors=Walsh HA, Botting NP |title=Purification and biochemical characterization of some of the properties of recombinant human kynureninase. |journal=Eur. J. Biochem. |volume=269 |issue= 8 |pages= 2069–74 |year= 2002 |pmid= 11985583 |doi=  10.1046/j.1432-1033.2002.02854.x|doi-access= }}
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=  10.1016/S0378-1119(97)00411-3}}
{{refend}}

== External links ==
* [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/Q16719 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Kynureninase

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[[Category:EC 3.7.1]]