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 α-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 α-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 α-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.
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September 01 2008
Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II
Qian Han;
Qian Han
1
*Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Tao Cai;
Tao Cai
†OIIB, NIDCR (National Institute of Dental and Craniofacial Research), National Institutes of Health, Bethesda, MD 20892-4322, U.S.A.
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Danilo A. Tagle;
Danilo A. Tagle
‡Neuroscience Center, NINDS (National Institute of Neurological Disorders and Stroke), National Institutes of Health, Bethesda, MD 20892-9525, U.S.A.
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Howard Robinson;
Howard Robinson
§Biology Department, Brookhaven National Laboratory, Upton, NY 11973, U.S.A.
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Jianyong Li
Jianyong Li
*Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, U.S.A.
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Publisher: Portland Press Ltd
Received:
July 03 2008
Accepted:
July 14 2008
Accepted Manuscript online:
July 14 2008
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biosci Rep (2008) 28 (4): 205–215.
Article history
Received:
July 03 2008
Accepted:
July 14 2008
Accepted Manuscript online:
July 14 2008
Citation
Qian Han, Tao Cai, Danilo A. Tagle, Howard Robinson, Jianyong Li; Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II. Biosci Rep 1 August 2008; 28 (4): 205–215. doi: https://doi.org/10.1042/BSR20080085
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