3DC1

Crystal structure of kynurenine aminotransferase II complex with alpha-ketoglutarate

Summary for 3DC1

• Entry DOI: 10.2210/pdb3dc1/pdb
• Descriptor: Kynurenine/alpha-aminoadipate aminotransferase mitochondrial, 2-OXOGLUTARIC ACID, GLYCEROL, ... (4 entities in total)
• Functional Keywords: alpha & beta protein, plp-dependent transferase, aminotransferase, multifunctional enzyme, pyridoxal phosphate, mitochondrion, transferase, transit peptide
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion (Potential): Q8N5Z0
• Total number of polymer chains: 4
• Total formula weight: 191212.87

Authors

Han, Q.,Cai, T.,Tagle, D.A.,Robinson, H.,Li, J. (deposition date: 2008-06-03, release date: 2008-07-29, Last modification date: 2023-11-15)

Primary citation

Han, Q.,Cai, T.,Tagle, D.A.,Robinson, H.,Li, J.
Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II
Biosci.Rep., 28:205-215, 2008

PubMed Abstract: 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.

PubMed: 18620547
DOI: 10.1042/BSR20080085

Experimental method

X-RAY DIFFRACTION (2.5 Å)