Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning.

ABSTRACT: 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 molecule exhibited an unusually high affinity for gaseous ligands, with a P₅₀ (partial pressure of O₂ at which hemoglobin is half-saturated) value for oxygen of 0.015 mmHg. Ngb-H64Q-CCC bound CO about 500 times more strongly than did hemoglobin. I

SUBMITTER: Azarov I 

PROVIDER: S-EPMC5206801 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature