The enzymology of nitric oxide in bacterial pathogenesis and resistance

Abstract

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.

How does a valine residue that modulates heme-NO binding kinetics in inducible NO synthase regulate enzyme catalysis?

“…Our study highlights an important role for heme pocket geometry in balancing multiple kinetic parameters in iNOS, which in turn balance its different catalytic activities. Our results also imply that the bacterial NOS enzymes, which typically conserve the Val to Ile mutation, might in some way take advantage of the consequent kinetic changes to function in various biological settings [49]. …”

Nitric oxide generation from heme/copper assembly mediated nitrite reductase activity

“…The classical biological source of NO is nitric oxide synthase (NOS) oxidation of L-arginine [11, 12]. This nitrite reductase chemistry represents an important alternative biological source of NO [1–4, 13].…”

Antioxidant Functions of Nitric Oxide Synthase in a Methicillin SensitiveStaphylococcus aureus

“…In these species, NOS-derived nitric oxide (NO) is involved in vasodilation, neurotransmission, and host defense [7, 13, 14], but the functions of bacterial NOS are still being defined. Recent genome sequencing has revealed that NOS-like protein exists in many bacteria including Streptomyces (StNOS), Deinococcus (DrNOS), Staphylococcus (SaNOS), and Bacillus (BsNOS) species [15]. Bacterial NOS enzymes are homologous with the mammalian NOS, but lack an associated NOS reductase and N-terminal β -hairpin hook that binds Zn 2+ , the dihydroxypropyl side chain of H 4 B, and the adjacent subunit of the oxygenase dimer [15–18].…”