Searching for DDAH inhibitors: S-nitroso-L-homocysteine is a chemical lead |
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Authors: | Knipp Markus Braun Oliver Vasák Milan |
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Institution: | Institute of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. knippy@bioc.unizh.ch |
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Abstract: | 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. |
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