Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, with no available
antidotal therapy. We introduce a potential treatment paradigm for CO poisoning, based on
near-irreversible binding of CO by an engineered human neuroglobin (Ngb). Ngb is a six-
coordinate hemoprotein, with the heme iron coordinated by two histidine residues. We
mutated the distal histidine to glutamine (H64Q) and substituted three surface cysteines with
less reactive amino acids to form a five-coordinate heme protein (Ngb-H64Q-CCC). This …

Background: Carbon monoxide (CO) poisoning is a leading cause of poisoning deaths
worldwide, with no available antidotal therapy. Neuroglobin (Ngb) is a six-coordinate
hemoprotein, with the heme iron coordinated by two histidine residues. We mutated the
distal histidine to glutamine (H64Q), combined with three surface thiol substitutions, forming
a five-coordinate heme protein (Ngb-H64Q-CCC). This molecule exhibits an unusually high
affinity for gaseous ligands, with a P50 value for oxygen of 0.05 mmHg. This finding informs …