Fast ferrous heme-NO oxidation in nitric oxide synthases.

Jesús Tejero (1) , J. Santolini (2) , Dennis J Stuehr (1)

1 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195
2 LSOD - Stress Oxydants et Détoxication

During catalysis, the heme in nitric oxide synthase (NOS) binds NO before releasing it to the environment. Oxidation of the NOS ferrous heme-NO complex by O2 is key for catalytic cycling, but the mechanism is unclear. We utilized stopped-flow methods to study the reaction of O2 with ferrous heme-NO complexes of inducible and neuronal NOS enzymes. We found that the reaction does not involve heme-NO dissociation, but instead proceeds by a rapid direct reaction of O2 with the ferrous heme-NO complex. This behavior is novel and may distinguish heme-thiolate enzymes, such as NOS, from related heme proteins.

Mots clés: enzyme mechanism; heme protein; heme-thiolate; nitric oxide; redox; FLASH-PHOTOLYSIS; CO BINDING; OXYGENASE DOMAIN; L-ARGININE; IN-VIVO; KINETICS; MECHANISM; TETRAHYDROBIOPTERIN; FLAVOHEMOGLOBIN; DIOXYGENASE

Domaines: Biochimie, Biologie Moléculaire

Jesús Tejero, J. Santolini, Dennis J Stuehr. Fast ferrous heme-NO oxidation in nitric oxide synthases.. FEBS Journal, 2009, 276 (16), pp.4505-14. ⟨10.1111/j.1742-4658.2009.07157.x⟩. ⟨cea-01234308⟩