Structural Insight into the Mechanism of Substrate Specificity of Aedes Kynurenine Aminotransferase

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Biochemistry

DOI:https://doi.org/10.1021/bi701800j· OSTI ID:959823

Han, Q; Gao, Y; Robinson, H; Li, J

Aedes aegypti kynurenine aminotransferase (AeKAT) is a multifunctional aminotransferase. It catalyzes the transamination of a number of amino acids and uses many biologically relevant a-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 {alpha}7-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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959823
• Report Number(s): BNL--82809-2009-JA
• Journal Information: Biochemistry, Journal Name: Biochemistry Vol. 47; ISSN 0006-2960; ISSN BICHAW
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ACETYLCHOLINE
AMINO ACIDS
AMINOTRANSFERASES
BIOSYNTHESIS
CRYSTAL STRUCTURE
CYSTEINE
ENZYMES
GLUTAMINE
HETEROCYCLIC ACIDS
HYDROXY COMPOUNDS
KYNURENINE
MOSQUITOES
PYRIDOXAL
QUINOLINES
RESIDUES
SPECIFICITY
SUBSTRATES
national synchrotron light source