犬尿喹啉酸（Kynurenic acid）是唯一已知天然生成的神经NMDA受体，这种化合物在大脑中的数量异常与多种精神疾病有关，包括精神分裂症。目前，研究者发现了KYNA合成酶的3D结构，该结果可能会使其成为新的药物靶标。
KYNA由一种名为 犬尿氨酸转氨酶II （KAT-II）的酶合成。弗吉尼亚科技大学的Jianyong Li及其同事们最近解析出了这种酶以及KAT-II与犬尿氨酸前体的复合物结构，且解析结果分辨率很高。
解出的结构有些令人惊讶，KAT-II的前65个氨基酸以一种特定方式折叠，使KAT-II的形状与其他相关转氨酶不同。论文作者认为，KAT-II代表了该转氨酶家族中的一种新型亚类。除了给合理的药物开发提供更详细的分子模型，该酶的这种特殊结构能使其成为理想的药物靶点，因为以它开发出的药物对其他相关酶类的影响非常低。
相关论文在线发表于2008年2月1日《生物化学杂志》（JBC）网站 (Vol. 283, No. 6)。 （来源：中科院广州生物医药与健康研究院）
（《生物化学杂志》（JBC），Vol. 283, Issue 6, 3567-3573, February 8, 2008，Qian Han, Jianyong Li）
生物谷推荐原始出处：
Originally published In Press as doi:10.1074/jbc.M708358200 on December 5, 2007
J. Biol. Chem., Vol. 283, Issue 6, 3567-3573, February 8, 2008
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.
