Ferryl haem protonation gates peroxidatic reactivity in globins

Radu Silaghi-Dumitrescu , Brandon J Reeder , Peter Nicholls , Chris E Cooper , Michael T Wilson (1)

1 Biological Sciences

Ferryl (Fe(IV)=O) species are involved in key enzymatic processes with direct biomedical relevance; among others, the uncontrolled reactivities of ferryl myoglobin and haemoglobin have been reported to be central to the pathology of rhabdomyolysis and subarachnoid haemorrhage. Rapid scan stopped-flow methods have been used to monitor the spectra of the ferryl species in myoglobin and haemoglobin as a function of pH. The ferryl forms of both proteins display an optical transition with pK~4.7 and this is assigned to protonation of the ferryl species itself. We also demonstrate for the first time a direct correlation between haemo(myo)globin ferryl reactivity and ferryl protonation status, simultaneously informing on chemical mechanism and toxicity and with broader biochemical implications.

Mots clés: Life Sciences

Radu Silaghi-Dumitrescu, Brandon J Reeder, Peter Nicholls, Chris E Cooper, Michael T Wilson. Ferryl haem protonation gates peroxidatic reactivity in globins. Biochemical Journal, 2007, 403 (3), pp.391-395. ⟨10.1042/BJ20061421⟩. ⟨hal-00478666⟩