Indirectly regulating nitric oxide

The structure of the enzyme DDAH that controls levels of arginine derivates offers the basis for designing selective indirect inhibitors of NO.

Tudor Toma(

Nitric oxide (NO) is a signalling molecule involved in a range of diseases and conditions, such as asthma, cancer and impotence. The natural levels of arginine derivates — which can inhibit nitric oxide synthase and decrease NO — are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH). In August Nature Structural Biology Judith Murray-Rust and colleagues from the School of Crystallography, Birkbeck College, London report the structure of the enzyme DDAH that may offer a new way of indirectly decreasing NO concentrations.

Murray-Rust et al. identified the crystal structure of a Pseudomonas aureus DDAH and found that this enzyme is a member of a structural superfamily of enzymes that use arginine or substituted arginine as a substrate. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a common reaction mechanism between DDAH and other superfamily members...

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