NADPH oxidase 5 (NOX5) interacts with and is regulated by calmodulin

Superoxide generation by NADPH oxidase 5 (NOX5) is regulated by Ca2+ through intramolecular activation of the C-terminal catalytic domain by the EF-hand-containing N-terminal regulatory domain. The C terminus contains a consensus calmodulin-binding domain (CaMBD), which, however, is not the binding site of the N-terminal regulatory domain. Here we show by pull down, cross-linking, fluorimetry and by enzymatic assays, that calmodulin binds to this CaMBD in a Ca(2+)dependent manner, changes its conformation and increases the Ca2+ sensitivity of the N terminus-regulated enzymatic activity. This mechanism represents an additional sophistication in the regulation of superoxide production by NOX5. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.