Crystal structures of Aedes aegypti kynurenine aminotransferase

  title={Crystal structures of Aedes aegypti kynurenine aminotransferase},
  author={Qian Han and Yi Gui Gao and Howard H Robinson and Haizhen Ding and Scott R. Wilson and Jianyong Li},
  journal={The FEBS Journal},
Aedes aegypti kynurenine aminotransferase (AeKAT) catalyzes the irreversible transamination of kynurenine to kynurenic acid, the natural antagonist of NMDA and 7‐nicotinic acetycholine receptors. Here, we report the crystal structure of AeKAT in its PMP and PLP forms at 1.90 and 1.55 Å, respectively. The structure was solved by a combination of single‐wavelength anomalous dispersion and molecular replacement approaches. The initial search model in the molecular replacement method was built with… 
Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.
The crystal structures of AeKAT in complex with its best amino acid substrates, glutamine and cysteine are reported, which is the first instance in which one pyridoxal 5-phosphate enzyme has been crystallized with Cysteine or glutamine forming external aldimine complexes, cysteinyl aldIMine and glutaminyl a Aldimine.
Crystal Structures of Aedes aegypti Alanine Glyoxylate Aminotransferase*
Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.
Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.
The hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group, and the discovery of two different ligands located simultaneously in the hKKAT I active center for the first time.
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.
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.
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.
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.
Cloning and molecular characterization of tick kynurenine aminotransferase (HlKAT) from Haemaphysalis longicornis (Acari: Ixodidae)
Results suggested that a specific HlKAT is present in tick and Hl kynurenine aminotransferase may play an important physiological role in H. longicornis.
Crystal Structure of MJ0684 from Methanococcus jannaschii, a Novel Archaeal Homolog of Kynurenine Aminotransferase
Structural observations imply that MJ0684 is a novel archaeal homolog of the subfamily Iγ kynurenine aminotransferase.


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.
Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate.
The thermostability of the enzyme is attained at least in part by the high content of Pro residues in the beta-turns and the marked increase in the number of salt bridges on the molecular surface compared with the mesophilic AspAT.
Purification and Characterization of Kynurenine Aminotransferase I from Human Brain
Immunotitration and immunoblotting analyses confirmed that KAT I is clearly distinct from both human KAT II and rat kynurenine‐pyruvate aminotransferase.
Isolation, characterization, and functional expression of kynurenine aminotransferase cDNA from the yellow fever mosquito, Aedes aegypti(1).
Northern analysis indicates that transcription of the AeKAT occurs at all stages during mosquito development, but higher levels of mRNA are observed during the pupal and adult stages, and may play an important physiological role in A. aegypti.
pH dependence, substrate specificity and inhibition of human kynurenine aminotransferase I.
It is demonstrated that hKAT-I can catalyze kynurenine to kynurenic acid under physiological pH conditions, indicates indo-3-pyruvate and cysteine as efficient inhibitors for hKat-I, and provides biochemical information about the substrate specificity and cosubstrate inhibition of the enzyme.
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