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Kynureninase

From Wikipedia, the free encyclopedia
kynureninase
Crystal structure ofHomo sapiens kynureninase.[1]
Identifiers
EC no.3.7.1.3
CAS no.9024-78-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDBPDBePDBsum
Gene OntologyAmiGO /QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
KYNU
Available structures
PDBOrtholog search:PDBeRCSB
List of PDB id codes

2HZP,3E9K

Identifiers
AliasesKYNU, KYNUU, kynureninase, VCRL2
External IDsOMIM:605197;MGI:1918039;HomoloGene:2925;GeneCards:KYNU;OMA:KYNU - orthologs
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[2]
Chromosome 2 (human)
Genomic location for KYNU
Genomic location for KYNU
Band2q22.2Start142,877,657bp[2]
End143,055,833bp[2]
Gene location (Mouse)
Chromosome 2 (mouse)
Chr.Chromosome 2 (mouse)[3]
Chromosome 2 (mouse)
Genomic location for KYNU
Genomic location for KYNU
Band2|2 BStart43,445,341bp[3]
End43,572,727bp[3]
RNA expression pattern
Bgee
HumanMouse (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
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 2: 43.45 – 43.57 Mb
PubMed search[4][5]
Wikidata
View/Edit HumanView/Edit Mouse

Kynureninase orL-Kynurenine hydrolase (KYNU) (EC3.7.1.3) is aPLP dependentenzyme that catalyses the cleavage ofkynurenine (Kyn) intoanthranilic acid (Ant). It can also act on3-hydroxykynurenine (to produce3-hydroxyanthranilate) and some other (3-arylcarbonyl)-alanines. Humans express one kynureninase enzyme that is encoded by theKYNUgene located on chromosome 2.[6][7]

KYNU is part of the pathway for thecatabolism ofTrp and the biosynthesis ofNADcofactors fromtryptophan (Trp).

Kynureninase catalyzes the following reaction:

L-kynurenine + H2O ↔anthranilate +L-alanine

Structure

[edit]

Kynureninase belongs to theclass V group ofaspartate 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

[edit]

In KYNU reaction, PLP facilitates Cβ-Cγ bond cleavage. The reaction follows the same steps as thetransamination reaction but does not hydrolyze thetautomerizedSchiff base. The proposed reaction mechanism involves an attack of an enzymenucleophile 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.
  KYNU
  PLP
  substrate names
  inorganic molecules
  3hAn's moiety
  Ala's moiety

References

[edit]
  1. ^abcPDB:2HZP​;Lima S, Khristoforov R, Momany C, Phillips RS (March 2007)."Crystal structure of Homo sapiens kynureninase".Biochemistry.46 (10):2735–44.doi:10.1021/bi0616697.PMC 2531291.PMID 17300176.
  2. ^abcGRCh38: Ensembl release 89: ENSG00000115919Ensembl, May 2017
  3. ^abcGRCm38: Ensembl release 89: ENSMUSG00000026866Ensembl, May 2017
  4. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  6. ^Alberati-Giani D, Buchli R, Malherbe P, Broger C, Lang G, Köhler C, Lahm HW, Cesura AM (July 1996)."Isolation and expression of a cDNA clone encoding human kynureninase".Eur. J. Biochem.239 (2):460–8.doi:10.1111/j.1432-1033.1996.0460u.x.PMID 8706755.
  7. ^Toma S, Nakamura M, Toné S, Okuno E, Kido R, Breton J, Avanzi N, Cozzi L, Speciale C, Mostardini M, Gatti S, Benatti L (May 1997)."Cloning and recombinant expression of rat and human kynureninase".FEBS Lett.408 (1):5–10.doi:10.1016/S0014-5793(97)00374-8.PMID 9180257.S2CID 36265922.
  8. ^PDB:3E9K​;Lima S, Kumar S, Gawandi V, Momany C, Phillips RS (January 2009). "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.doi:10.1021/jm8010806.PMID 19143568.

Further reading

[edit]

External links

[edit]
  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Kynureninase
PDB gallery
  • 3e9k: Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex
    3e9k: Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex
  • 2hzp: Crystal Structure of Homo Sapiens Kynureninase
    2hzp: Crystal Structure of Homo Sapiens Kynureninase
Mitochondrial proteins
Outer membrane
fatty acid degradation
tryptophan metabolism
monoamine neurotransmitter
metabolism
Intermembrane space
Inner membrane
oxidative phosphorylation
pyrimidine metabolism
mitochondrial shuttle
steroidogenesis
other
Matrix
citric acid cycle
anaplerotic reactions
urea cycle
alcohol metabolism
Other/to be sorted
Mitochondrial DNA
Complex I
Complex III
Complex IV
ATP synthase
tRNA
Essential amino acids are in Capitals
Kacetyl-CoA
LYSINE
LEUCINE
TRYPTOPHAN
PHENYLALANINEtyrosine
  • (see below)
G
G→pyruvate
citrate
glycineserine
alanine
cysteine
threonine
G→glutamate
α-ketoglutarate
HISTIDINE
proline
arginine
alpha-ketoglutarate→TCA
Other
G→propionyl-CoA
succinyl-CoA
VALINE
ISOLEUCINE
METHIONINE
THREONINE
succinyl-CoA→TCA
G→fumarate
PHENYLALANINEtyrosine
G→oxaloacetate
asparagineaspartate
Hydrolases: carbon-carbon (EC 3.7)
3.7.1
Activity
Regulation
Classification
Kinetics
Types
Portal:
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