The enzymology of nitric oxide in bacterial pathogenesis and resistance

Mammalian NOSs (nitric oxide synthases) are haem-based monoxygenases that oxidize the amino acid arginine to the intracellular signal and protective cytotoxin nitric oxide (NO). Certain strains of mostly Gram-positive bacteria contain homologues of the mammalian NOS catalytic domain that can act as NOSs when suitable reductants are supplied. Crystallographic analyses of bacterial NOSs, with substrates and haem-ligands, have disclosed important features of assembly and active-centre chemistry, both general to the NOS family and specific to the bacterial proteins. The slow reaction profiles and especially stable haem-oxygen species of NOSs derived from bacterial thermophiles have facilitated the study of NOS reaction intermediates. Functionally, bacterial NOSs are distinct from their mammalian counterparts. In certain strains of Streptomyces, they participate in the biosynthetic nitration of plant toxins. In the radiation-resistant bacterium Deinococcus radiodurans, NOSs are also likely to be involved in biosynthetic nitration reactions, but, furthermore, appear to play an important role in the recovery from damage induced by UV radiation.