Nitric oxide reductase (NOR) (NOR)

Nitric oxide reductase (NOR) is an essential microbial enzyme that catalyzes the reduction of nitric oxide (NO) into nitrous oxide (N2O) as a key step in the denitrification pathway [1][16]. While absent in humans, this enzyme is vital for the survival of many pathogenic bacteria, such as Pseudomonas aeruginosa and Neisseria meningitidis, as well as certain fungi, because it detoxifies the NO produced by the host's innate immune system [15][22]. Host macrophages generate NO as a cytotoxic defense; however, pathogens utilize NOR to neutralize this molecule, thereby facilitating persistent infection and biofilm formation [10][20]. This makes NOR a promising therapeutic target for the development of novel antimicrobial agents, particularly against multi-drug resistant pathogens [6][8]. Most microbial NORs are membrane-integrated metalloenzymes within the heme-copper oxidase (HCO) superfamily, structurally similar to human terminal oxidases [16][21]. Current pharmacological research is focused on identifying small-molecule inhibitors that can selectively bind the NOR active site to induce lethal NO accumulation within the pathogen without interfering with human mitochondrial respiration [6][23]. The primary challenge in drug development remains the high level of structural conservation between microbial NOR and human Cytochrome c Oxidase, necessitating exceptional selectivity to avoid off-target host toxicity [19][21].

Other names

Nitric oxide (NO) reductaseCytochrome c-dependent nitric oxide reductase (cNOR)Quinol-dependent nitric oxide reductase (qNOR)Nitrogen-monoxide reductaseNitrous-oxide:acceptor oxidoreductase (NO-forming)Flavorubredoxin (NorVW)Cytochrome P450nor (fungal type)

Inhibition of the enzymatic reduction of nitric oxide (NO) to nitrous oxide (N2O), leading to the accumulation of toxic reactive nitrogen species (RNS) and the subsequent inhibition of microbial respiration and survival.