Abstract
During the anoxic stages of the early Earth, nitric oxide (NO) served as a major nitrogen source for prokaryotes, which, against a backdrop of an increasingly oxygen-rich atmosphere, evolved NO signaling mechanisms for processes including the regulation of communal behavior (Plate and Marletta, 2012). In humans, NO lowers blood pressure, acts as neurotransmitter, and activates macrophages during immune responses (Farah et al., 2018). Animal NO-sensing proteins share structural similarity with those of early prokaryotes, as exemplified by the activation of soluble guanylate cyclases (sGCs), in which a heme-containing domain enables NO sensing by the heme NO/oxygen (H-NOX), thus indicating ancient evolutionary origin.
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