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NO Way Back Is the neuronal nitric oxide synthase the evolutionary link between primitive bacterial nitric oxide synthase-like proteins and mammalian nitric oxide synthases?



NO Way Back Is the neuronal nitric oxide synthase the evolutionary link between primitive bacterial nitric oxide synthase-like proteins and mammalian nitric oxide synthases?



FASEB Journal 17(4-5): Abstract No 119 9



We have recently characterized a bacterial NOS-like protein from Deinococcus radiodurans (deiNOS), which is dimeric and could produce NO in a hetero-dimeric setting despite its missing a large part of the N-terminal region of Nitric Oxide Synthase (NOS). Notably, deletion of this region causes complete monomerization and inactivation of mammalian inducible NOS as well as endothelial NOS. To examine whether N-terminally truncated rat neuronal NOS (nNOS) could mimic deiNOS, we generated the analogous N-terminally deleted nNOS oxygenase (delta349nNOSoxy) and full-length (delta349nNOSFl) proteins. Indeed. the gel-filtration profile of the delta349nNOSoxy revealed that it was 83% dimeric. Mammalian NOSs fail to bind tetrahydrofolate (THF), the predominant pteridine present in bacteria, plausibly due to steric hindrance posed by the N-terminal hook. However, our N-terminally truncated nNOS proteins could indeed bind THF like in the bacterial NOSs. Further, the delta349nNOSFl could produce NO in the presence of THF much like deiNOS and Bacillus Subtilis NOS under complementation from electron donating reductases. Overall, the structural and catalytic resemblance observed for the delta349nNOS with the analogous bacterial NOS like proteins, suggest that such primitive NOSs have probably evolved into the higher mammalian NOSs through nNOS and its unique repertoire of N-terminally truncated splice variants.

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