Author: Knipp, Markus

Source: Letters in Drug Design & Discovery, Volume 4, Number 8, December 2007 , pp. 570-579(10)

Publisher: Bentham Science Publishers

Abstract:

The cysteine hydrolase N ω,N ω-dimethyl-L-arginine dimethylaminohydrolase-1 (DDAH-1) is an important regulator of NO production through the degradation of endogenous Nω-methylated arginines, that are competitive inhibitors for nitric oxide synthase (NOS). Consequently, DDAH-1 is a target for pharmacological drug design to regulate NO production. The appearance of a second isoform DDAH-2, which was assigned through sequence comparison, requires detailed knowledge about the properties of both proteins. This study represents the first attempt for a structural and functional characterization of DDAH-2. However, lack in enzymatic activity together with structural consideration based on a homology model places the designation as a DDAH enzyme into question. On the other hand, it is shown that DDAH-2 is a substrate for two protein-arginine methyltransferases, CARM-1 and PRMT-6, which supports the participation of DDAH-2 in the metabolism of side-chain methylated arginines.

Keywords: Arginine methylation; CARM-1; DDAH; Dimethylarginine dimethylaminohydrolase; g6a; PRMT-6

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157018007782794572

Publication date: 2007-12-01

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• Letters in Drug Design & Discovery publishes original letters on all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of Internet technology for both the submission and review of manuscripts. The journal is essential reading to all pharmaceutical scientists involved in research in drug design and discovery.

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