Crystal structure of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3 at 2.20 Å resolution

  title={Crystal structure of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3 at 2.20 {\AA} resolution},
  author={Hyongi Chon and Hiroyoshi Matsumura and Yuichi Koga and Kazufumi Takano and Shigenori Kanaya},
  journal={Proteins: Structure},
Introduction. Kynurenine aminotransferase (KAT; EC. is an enzyme that catalyzes the irreversible transamination of L-kynurenine (L-Kyn) to produce kynurenic acid (KA). L-Kyn is a major metabolite in the degradation pathway of tryptophan, and KA acts as an endogenous antagonist of all three ionotropic excitatory amino acid receptors in the central nervous system. Enormous attention has recently been paid to structural and functional studies of KAT, because alteration in the endogenous… 
Crystal Structure of Human Kynurenine Aminotransferase II*
The protein architecture of hKAT-II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)-dependent enzymes, and it is proposed that hKat-II represents a novel subclass in the Fold- type I enzymes because of the unique folding of its first 65 N-terminal residues.
Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution
The crystal structure of full-length PLP-form hKAT-II was determined at 1.83 Å resolution, the highest available, and reveals an aldimine linkage between PLP and Lys263, as well as the active site residues, which characterize the fold-type IPLP-dependent enzymes.
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains
The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.
Biochemical and Structural Properties of Mouse Kynurenine Aminotransferase III
It is established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60°C.
Characteristic Features of Kynurenine Aminotransferase Allosterically Regulated by (Alpha)-Ketoglutarate in Cooperation with Kynurenine
The combined data lead to the conclusion that PhKAT probably is regulated by allosteric control machineries, with 2OG as theAllosteric inhibitor.
Thermal stability, pH dependence and inhibition of four murine kynurenine aminotransferases
The characteristics reported here could be used to develop specific assay methods for each of the four murine KATs and identify which KAT is affected in mouse models for research and to develop small molecule drugs for prevention and treatment of KAT-involved human diseases.
Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis.
Crystal Structure of Human Kynurenine Aminotransferase II, a Drug Target for the Treatment of Schizophrenia*
The structure of human KAT II is solved by means of the single-wavelength anomalous dispersion method at 2.3-Å resolution and reveals a novel antiparallel strand-loop-strand motif that forms an unprecedented intersubunit β-sheet in the functional hKAT II dimer.
Mechanism for multiple‐substrates recognition of α‐aminoadipate aminotransferase from Thermus thermophilus
The results indicate that AAA‐AT can recognize various kinds of substrates using the mobile α2 helix and that intersubunit‐electrostatic interactions contribute to the elevated thermostability of this enzyme.


Overproduction and preliminary crystallographic study of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3.
  • H. Chon, H. Matsumura, S. Kanaya
  • Chemistry
    Acta crystallographica. Section F, Structural biology and crystallization communications
  • 2005
Gel-filtration chromatography showed that Ph-KAT II exists as a homodimer and exhibited enzymatic activity that catalyzes the transamination of L-kynurenine to produce kynurenic acid.
Crystal Structure of Human Kynurenine Aminotransferase I*
The data reveal a key structural role of Glu27, providing a molecular basis for the reported loss of enzymatic activity displayed by the equivalent Glu → Gly mutation in KAT-I of spontaneously hypertensive rats.
Characterization of rat brain kynurenine aminotransferases I and II
A simple methodology for the simultaneous determination of the two KYNA‐producing enzymes in small rat brain tissue samples is described and baseline values for future work in experimentally challenged animals are provided.
Genomic organization and expression analysis of mouse kynurenine aminotransferase II, a possible factor in the pathophysiology of Huntington's disease
Knowing the genomic organization, the isoform tissue-specific expression patterns, the chromosomal localization of mKat-2, and the reagents generated here, will provide the tools for further studies and allow generation and characterization of mice that are nullizygous for m Kat-2.
Two kynurenine aminotransferases in human brain
Crystal Structures of Glutamine:Phenylpyruvate Aminotransferase from Thermus thermophilus HB8
The following three-dimensional structures of three forms of glutamine:phenylpyruvate aminotransferase from Thermus thermophilus HB8 have been determined and represent the first x-ray analysis of the
Kynurenine metabolism in Alzheimer's disease
The present data indicate an elevated kynurenine metabolism in AD brain and a marked increase of KYNA in the caudate nucleus and putamen may compensate the hyperactivity of the striato-frontal loop in AD brains.