Kynurenic acid is the only known naturally occurring blocker of neuronal NMDA receptors, and abnormal amounts of this chemical in the brain are associated with several psychiatric disorders, including schizophrenia. Researchers have now discovered the 3D structure of the enzyme that synthesizes KYNA, which may potentially lead to new drug targets.
KYNA is created by an enzyme called kynurenine aminotransferase II (KAT-II). Jianyong Li and colleagues at Virginia Tech have now solved the structure of both the enzyme and KAT-II complexed with the precursor chemical kynurenine at high resolution.
The structures revealed a bit of a surprise in that the first 65 amino acids of KAT-II fold in a unique way, giving KAT-II a different shape than related aminotransferase enzymes. The authors propose that KAT-II represents a novel subclass of its enzyme family.
So, in addition to providing a detailed molecular model for rational drug development, the unusual structure of this enzyme suggests it would be an ideal drug target since the risks of drugs affecting related enzymes would be greatly reduced.
This research was recently published in the Journal of Biological Chemistry. Corresponding Author: Jianyong Li, Department of Biochemistry, Virginia Tech, Blacksburg, VA.
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