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J. Biol. Chem., Vol. 283, Issue 6, 3567-3573, February 8, 2008

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Crystal Structure of Human Kynurenine Aminotransferase II^*

Qian Han, Howard Robinson, and Jianyong Li¹

From the Department of Biochemistry, Virginia Tech University, Blacksburg, Virginia 24061 and the Biology Department, Brookhaven National Laboratory, Upton, New York 11973

Human kynurenine aminotransferase II (hKAT-II) efficiently catalyzes the transamination of knunrenine to kynurenic acid (KYNA). KYNA is the only known endogenous antagonist of N-methyl-D-aspartate (NMDA) receptors and is also an antagonist of 7-nicotinic acetylcholine receptors. Abnormal concentrations of brain KYNA have been implicated in the pathogenesis and development of several neurological and psychiatric diseases in humans. Consequently, enzymes involved in the production of brain KYNA have been considered potential regulatory targets. In this article, we report a 2.16Å crystal structure of hKAT-II and a 1.95Å structure of its complex with kynurenine. The protein architecture of hKAT-II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)-dependent enzymes. In comparison with all subclasses of fold-type I-PLP-dependent enzymes, we propose that hKAT-II represents a novel subclass in the fold-type I enzymes because of the unique folding of its first 65 N-terminal residues. This study provides a molecular basis for future effort in maintaining physiological concentrations of KYNA through molecular and biochemical regulation of hKAT-II.

Received for publication, October 9, 2007 , and in revised form, November 20, 2009.

The atomic coordinates and structure factors (code 2QLR and 2R2N) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Grant R01 AI 44399 from the National Institutes of Health and was carried out in part at the National Synchrotron Light Source, Brookhaven National Laboratory. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biochemistry, Virginia Tech, Blacksburg, VA 24061. Tel.: 540-231-1182; Fax: 540-231-9070; E-mail: lij{at}vt.edu.

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				Q. Han, H. Robinson, T. Cai, D. A. Tagle, and J. Li Biochemical and Structural Properties of Mouse Kynurenine Aminotransferase III Mol. Cell. Biol., February 1, 2009; 29(3): 784 - 793. [Abstract] [Full Text] [PDF]