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1-L-甲基色氨酸比 1-D-甲基色氨酸更有效地抑制脊椎动物 IDO2 酶。

1-L-methyltryptophan is a more effective inhibitor of vertebrate IDO2 enzymes than 1-D-methyltryptophan.

机构信息

Laboratory of Biochemistry, Department of Applied Science, Faculty of Science, National University Corporation Kochi University, Kochi 780-8520, Japan.

出版信息

Comp Biochem Physiol B Biochem Mol Biol. 2010 Sep;157(1):10-5. doi: 10.1016/j.cbpb.2010.04.006. Epub 2010 Apr 23.

DOI:10.1016/j.cbpb.2010.04.006
PMID:20399882
Abstract

1-D-methyltryptophan (D-1MT) is an effective anti-cancer agent in mouse tumour models. It has been suggested to be a selective inhibitor of the recently described tryptophan-degrading enzyme indoleamine 2,3-dioxygenase 2 (IDO2) rather than the closely related enzyme IDO1. We found that mammalian (mouse, opossum and platypus), chicken, frog, and fish IDO2 could be functional tryptophan-catabolising enzymes. The characteristics of pH-dependent activity and inhibitor selectivity were conserved amongst the vertebrate IDO2 proteins tested. Like IDO1 enzymes, the enzymatic activity of all IDO2s was inhibited by L-1MT but not by D-1MT in a cell-free assay. When IDO2s were expressed in mammalian cells, L-1MT was also a better inhibitor than D-1MT.

摘要

1-D-甲基色氨酸(D-1MT)是一种在小鼠肿瘤模型中有效的抗癌药物。它被认为是最近描述的色氨酸降解酶吲哚胺 2,3-双加氧酶 2(IDO2)的选择性抑制剂,而不是密切相关的酶 IDO1。我们发现哺乳动物(鼠、负鼠和鸭嘴兽)、鸡、青蛙和鱼的 IDO2 可以作为功能性色氨酸分解代谢酶。在测试的脊椎动物 IDO2 蛋白中,pH 依赖性活性和抑制剂选择性的特征是保守的。与 IDO1 酶一样,所有 IDO2 酶的酶活性在无细胞测定中均被 L-1MT 而非 D-1MT 抑制。当 IDO2 表达在哺乳动物细胞中时,L-1MT 也是比 D-1MT 更好的抑制剂。

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