Substrate Specificity and Structure of Human aminoadipate aminotransferase/kynurenine aminotransferase II

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Bioscience Reports

OSTI ID:980580

Han, Q; Cai, T; Tagle, D; Robinson, H; Li, J

KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to alpha-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested alpha-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with alpha-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15-33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 980580
• Report Number(s): BNL--93498-2010-JA
• Journal Information: Bioscience Reports, Journal Name: Bioscience Reports Journal Issue: 4 Vol. 28; ISSN 0144-8463; ISSN BRPTDT
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AFFINITY
AMINO ACIDS
AMINOTRANSFERASES
BRAIN
CONFORMATIONAL CHANGES
EFFICIENCY
ELEMENTS
ENZYMES
FUNCTIONALS
HUMAN POPULATIONS
INFORMATION
KINETICS
KYNURENINE
RESIDUES
SCREENING
SPECIFICITY
SUBSTRATES
national synchrotron light source