Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase

Biochemistry
Qian HanJianyong Li

Abstract

Aedes aegypti kynurenine aminotransferase (AeKAT) is a multifunctional aminotransferase. It catalyzes the transamination of a number of amino acids and uses many biologically relevant alpha-keto acids as amino group acceptors. AeKAT also is a cysteine S-conjugate beta-lyase. The most important function of AeKAT is the biosynthesis of kynurenic acid, a natural antagonist of NMDA and alpha7-nicotinic acetylcholine receptors. Here, we report the crystal structures of AeKAT in complex with its best amino acid substrates, glutamine and cysteine. Glutamine is found in both subunits of the biological dimer, and cysteine is found in one of the two subunits. Both substrates form external aldemines with pyridoxal 5-phosphate in the structures. This 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 aldimine. All the units with substrate are in the closed conformation form, and the unit without substrate is in the open form, which suggests that the binding of substrate induces the conformation change of AeKAT. By comparing the active site residues of the AeKAT-cysteine structure with those of the human KAT I...Continue Reading

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Citations

Oct 15, 2009·Cellular and Molecular Life Sciences : CMLS·Qian HanJianyong Li
Nov 26, 2008·Molecular and Cellular Biology·Qian HanJianyong Li
Oct 28, 2008·Current Opinion in Structural Biology·Franca RossiMenico Rizzi
May 16, 2009·Molecular and Biochemical Parasitology·Daniela MarcianoCristina Nowicki

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