Diversity and Complexity of flavodiiron NO/O2 reductases

Abstract

Flavodiiron proteins (FDPs) are a family of enzymes endowed with nitric oxide (NO) or oxygen reductase activities, forming the innocuous nitrous oxide (N₂O) or water molecules, respectively. FDPs are widespread in the three life kingdoms, and have a modular nature, being each monomer minimally constituted by a metallo-β-lactamase-like domain containing a catalytic diiron center, followed by a flavodoxin one, with a flavin mononucleotide (FMN). Since their discovery, additional domains have been found in FDPs, attached to the C-terminus, and containing either extra metal (iron) centers or extra flavin binding modules. Following an extensive analysis of genomic databases, we identified novel domain compositions, and propose a new Classification of FDPs in eight Classes based on the nature and number of extra domains.