2r5e | pdb_00002r5e
Aedes kynurenine aminotransferase in complex with glutamine
Structural highlights
FunctionKAT_AEDAE Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA) (PubMed:12110301, PubMed:15556614). Also catalyzes the irreversible transamination of several amino acids including cysteine, tyrosine, glutamine, methionine, histidine and phenylalanine (PubMed:15556614). Can use various keto-acids as the amino group acceptor (PubMed:15556614, PubMed:12110301).[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAedes 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-phenylalanine structure, we determined that Tyr286 in AeKAT is changed to Phe278 in human KAT I, which may explain why AeKAT transaminates hydrophilic amino acids more efficiently than human KAT I does. Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.,Han Q, Gao YG, Robinson H, Li J Biochemistry. 2008 Feb 12;47(6):1622-30. Epub 2008 Jan 11. PMID:18186649[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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