Ferryl haem protonation gates peroxidatic reactivity in globins
Ferryl haem protonation gates peroxidatic reactivity in globins
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DOI：
10.1042/bj20061421
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发表时间：
2007-05-01
影响因子：
4.1
通讯作者：
Wilson, Michael T.
中科院分区：
文献类型：
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作者：
Silaghi-Dumitrescu, Radu;Reeder, Brandon J.;Wilson, Michael T.
铁基(Fe(IV)=O)参与关键的酶过程，具有直接的生物医学意义；据报道，铁基Mb(肌红蛋白)和Hb(血红蛋白)的不受控制的反应是横纹肌溶解和蛛网膜下腔出血的主要病理机制。用快速扫描停流法监测了Mb和Hb中铁物种的光谱随pH的变化。这两种蛋白质的铁基形式都表现出一个光学跃迁，pK类似于4.7，这被认为是铁基物种本身的质子化。我们还首次证明了Hb/Mb铁基反应性和铁质子化状态之间的直接关联，同时提供了化学机制和毒性信息，并具有更广泛的生物化学意义。
Ferryl (Fe(IV) = O) species are involved in key enzymatic processes with direct biomedical relevance; among others, the uncontrolled reactivities of ferryl Mb (myoglobin) and Hb (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 Mb and Hb as a function of pH. The ferryl forms of both proteins display an optical transition with pK similar to 4.7, and this is assigned to protonation of the ferryl species itself. We also demonstrate for the first time a direct correlation between Hb/Mb ferryl reactivity and ferryl protonation status, simultaneously informing on chemical mechanism and toxicity and with broader biochemical implications.