Knipp Markus, Braun Oliver, Vasák Milan
Institute of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
J Am Chem Soc. 2005 Mar 2;127(8):2372-3. doi: 10.1021/ja0430200.
The cysteine-hydrolase dimethylargininase-1 (DDAH-1) is an important regulator of NO production in mammalian tissue for which the availability of an inhibitor for clinics and research would be most appreciated. While studying the effect of the endogenously occurring S-nitroso-l-homocysteine on DDAH-1, an unusual N-thiosulfoximide modification was identified in the active site of the enzyme. Thus, S-nitroso-l-homocysteine in combination with the mechanism proposed herein offers a basis for the rational design of DDAH inhibitors.
半胱氨酸水解酶二甲基精氨酸酶-1（DDAH-1）是哺乳动物组织中一氧化氮（NO）生成的重要调节因子，若能有用于临床和研究的抑制剂，将非常受欢迎。在研究内源性S-亚硝基-L-高半胱氨酸对DDAH-1的影响时，在该酶的活性位点发现了一种不寻常的N-硫代磺酰亚胺修饰。因此，S-亚硝基-L-高半胱氨酸与本文提出的机制相结合，为合理设计DDAH抑制剂提供了基础。
