kynurenine—oxoglutarate transaminase

{{infobox enzyme

| Name = kynurenine-oxoglutarate transaminase

| EC_number = 2.6.1.7

| CAS_number = 9030-38-0

| GO_code = 0016212

| image = 4wlh.jpg

| width = 270

| caption = Kynurenine aminotransferase-I homodimer, Human

}}

In enzymology, a kynurenine-oxoglutarate transaminase ({{EC number|2.6.1.7}}) is an enzyme that catalyzes the chemical reaction

:{{sc|L}}-kynurenine + 2-oxoglutarate {{eqm}} 4-(2-aminophenyl)-2,4-dioxobutanoate + {{sc|L}}-glutamate

Thus, the two substrates of this enzyme are Kynurenine and 2-oxoglutarate, whereas its two products are 4-(2-aminophenyl)-2,4-dioxobutanoate and Glutamate. The former product is an unstable α-oxo acid that quickly undergoes intramolecular cyclization to form kynurenic acid.{{cite journal | vauthors = Han Q, Cai T, Tagle DA, Robinson H, Li J | title = Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II | journal = Bioscience Reports | volume = 28 | issue = 4 | pages = 205–15 | date = August 2008 | pmid = 18620547 | pmc = 2559858 | doi = 10.1042/BSR20080085 }}

This enzyme belongs to the family of transferases, to be specific, the transaminases, that transfer nitrogenous groups. The systematic name of this enzyme class is {{sc|L}}-kynurenine:2-oxoglutarate aminotransferase. Other names in common use include kynurenine transaminase (cyclizing), kynurenine 2-oxoglutarate transaminase, kynurenine aminotransferase, and {{sc|L}}-kynurenine aminotransferase. This enzyme participates in tryptophan metabolism. It employs one cofactor, pyridoxal phosphate.

KYAT1, AADAT (aka KYAT2), and KYAT3 are examples of enzymes of this class. GOT2 (aka KYAT4) is also believed to catalyze the above reaction.{{cite journal | vauthors = Guidetti P, Amori L, Sapko MT, Okuno E, Schwarcz R | title = Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain | journal = Journal of Neurochemistry | volume = 102 | issue = 1 | pages = 103–11 | date = July 2007 | pmid = 17442055 | doi = 10.1111/j.1471-4159.2007.04556.x | s2cid = 20413002 | doi-access = }}

Structural studies

As of early 2009, 18 structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1X0M}}, {{PDB link|1YIY}}, {{PDB link|1YIZ}}, {{PDB link|1W7L}}, {{PDB link|1W7M}}, {{PDB link|1W7N}}, {{PDB link|3E2F}}, {{PDB link|3E2Y}}, {{PDB link|3E2Z}}, {{PDB link|2ZJG}}, {{PDB link|2YGZ}}, {{PDB link|2Z61}}, {{PDB link|2R5C}}, {{PDB link|2R2N}}, {{PDB link|2R5E}}, {{PDB link|3B46}}, {{PDB link|3DC1}}, and {{PDB link|2QLN}}.

References

{{cite journal | vauthors = Bonner DM, Jakoby WB | title = Kynurenine transaminase from neurospora | journal = The Journal of Biological Chemistry | volume = 221 | issue = 2 | pages = 689–95 | date = August 1956 | doi = 10.1016/S0021-9258(18)65181-6 | doi-access = free | pmid = 13357462 }}
{{cite journal | vauthors = Mason M | title = Kynurenine transaminase of rat kidney; a study of coenzyme dissociation | journal = The Journal of Biological Chemistry | volume = 227 | issue = 1 | pages = 61–8 | date = July 1957 | doi = 10.1016/S0021-9258(18)70795-3 | doi-access = free | pmid = 13449053 }}
{{cite journal | vauthors = Rossi F, Han Q, Li J, Li J, Rizzi M | title = Crystal structure of human kynurenine aminotransferase I | journal = The Journal of Biological Chemistry | volume = 279 | issue = 48 | pages = 50214–20 | date = November 2004 | pmid = 15364907 | doi = 10.1074/jbc.M409291200 | doi-access = free }}
{{cite journal | vauthors = Chon H, Matsumura H, Koga Y, Takano K, Kanaya S | title = Crystal structure of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3 at 2.20 A resolution | journal = Proteins | volume = 61 | issue = 3 | pages = 685–8 | date = November 2005 | pmid = 16138312 | doi = 10.1002/prot.20614 | s2cid = 35477005 | doi-access = free }}
{{cite journal | vauthors = Han Q, Gao YG, Robinson H, Ding H, Wilson S, Li J | title = Crystal structures of Aedes aegypti kynurenine aminotransferase | journal = The FEBS Journal | volume = 272 | issue = 9 | pages = 2198–206 | date = May 2005 | pmid = 15853804 | doi = 10.1111/j.1742-4658.2005.04643.x | s2cid = 38329597 | doi-access = }}
{{cite journal | vauthors = Han Q, Robinson H, Cai T, Tagle DA, Li J | title = Biochemical and structural properties of mouse kynurenine aminotransferase III | journal = Molecular and Cellular Biology | volume = 29 | issue = 3 | pages = 784–93 | date = February 2009 | pmid = 19029248 | pmc = 2630683 | doi = 10.1128/MCB.01272-08 }}
{{cite journal | vauthors = Han Q, Robinson H, Li J | title = Crystal structure of human kynurenine aminotransferase II | journal = The Journal of Biological Chemistry | volume = 283 | issue = 6 | pages = 3567–73 | date = February 2008 | pmid = 18056995 | doi = 10.1074/jbc.M708358200 | doi-access = free }}
{{cite journal | vauthors = Rossi F, Garavaglia S, Montalbano V, Walsh MA, Rizzi M | title = Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia | journal = The Journal of Biological Chemistry | volume = 283 | issue = 6 | pages = 3559–66 | date = February 2008 | pmid = 18056996 | doi = 10.1074/jbc.M707925200 | doi-access = free }}
{{cite journal | vauthors = Han Q, Cai T, Tagle DA, Robinson H, Li J | title = Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II | journal = Bioscience Reports | volume = 28 | issue = 4 | pages = 205–15 | date = August 2008 | pmid = 18620547 | pmc = 2559858 | doi = 10.1042/BSR20080085 }}
{{cite journal | vauthors = Han Q, Gao YG, Robinson H, Li J | title = Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase | journal = Biochemistry | volume = 47 | issue = 6 | pages = 1622–30 | date = February 2008 | pmid = 18186649 | pmc = 2858008 | doi = 10.1021/bi701800j }}
{{cite journal | vauthors = Wogulis M, Chew ER, Donohoue PD, Wilson DK | title = Identification of formyl kynurenine formamidase and kynurenine aminotransferase from Saccharomyces cerevisiae using crystallographic, bioinformatic and biochemical evidence | journal = Biochemistry | volume = 47 | issue = 6 | pages = 1608–21 | date = February 2008 | pmid = 18205391 | doi = 10.1021/bi701172v }}

Category:EC 2.6.1

Category:Enzymes of known structure

Category:Pyridoxal phosphate enzymes

kynurenine—oxoglutarate transaminase

Structural studies

References

Further reading