Searching for DDAH inhibitors: S-nitroso-L-homocysteine is a chemical lead.
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.
Knipp
Markus
M
Institute of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. knippy@bioc.unizh.ch
Braun
Oliver
O
Vasák
Milan
M
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008970:Molecular Weight; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
D004791:Enzyme Inhibitors; D006710:Homocysteine; C079202:S-nitrosohomocysteine; D000581:Amidohydrolases; C059999:dimethylargininase