煤氣中毒是由于血液中的血紅蛋白和煤氣中的一氧化碳結(jié)合造成的,。不過(guò)英國(guó)研究人員發(fā)現(xiàn),,在一氧化碳濃度較低的時(shí)候,血紅蛋白可以通過(guò)改變自身形狀阻止一氧化碳與其結(jié)合,從而避免中毒,。
英國(guó)利物浦大學(xué)的研究人員介紹說(shuō),,對(duì)包括人類在內(nèi)的許多生物而言,機(jī)體組織的新陳代謝本身都會(huì)產(chǎn)生一定量的一氧化碳,,為什么生物沒有因?yàn)檫@些一氧化碳而中毒,,成為研究人員關(guān)注的問(wèn)題。
本來(lái),,血紅蛋白的形狀非常適合與一氧化碳分子結(jié)合,,但研究人員發(fā)現(xiàn),如果血紅蛋白探測(cè)到機(jī)體釋放的少量一氧化碳,,它就會(huì)釋放出一股能量,,改變自己的形狀,通過(guò)這種方式阻止一氧化碳與其結(jié)合,。但如果一氧化碳濃度太高,,這種手段也無(wú)法防止中毒。
研究人員認(rèn)為,,可以在這一發(fā)現(xiàn)的基礎(chǔ)上開發(fā)一種生物感應(yīng)器,,專門用于對(duì)一氧化碳?xì)怏w含量非常敏感的地方,探測(cè)一氧化碳濃度的微小變化,。
研究報(bào)告已經(jīng)發(fā)表在美國(guó)《國(guó)家科學(xué)院院刊》(PNAS)上,。(生物谷 Bioon.com)
doi:10.1073/pnas.1109051108
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PMID:
Carbon monoxide poisoning is prevented by the energy costs of conformational changes in gas-binding haemproteins
Antonyuk, Svetlana V.; Rustage, Neil; Petersen, Christine A.; Arnst, Jamie L.; Heyes, Derren J.; Sharma, Raman; Berry, Neil G.; Scrutton, Nigel S.; Eady, Robert R.; Andrew, Colin R.; Hasnain, S. Samar
Carbon monoxide (CO) is a product of haem metabolism and organisms must evolve strategies to prevent endogenous CO poisoning of haemoproteins. We show that energy costs associated with conformational changes play a key role in preventing irreversible CO binding. AxCYTcp is a member of a family of haem proteins that form stable 5c–NO and 6c–CO complexes but do not form O2 complexes. Structure of the AxCYTcp–CO complex at 1.25 Å resolution shows that CO binds in two conformations moderated by the extent of displacement of the distal residue Leu16 toward the haem 7-propionate. The presence of two CO conformations is confirmed by cryogenic resonance Raman data. The preferred linear Fe–C–O arrangement (170 ± 8°) is accompanied by a flip of the propionate from the distal to proximal face of the haem. In the second conformation, the Fe–C–O unit is bent (158 ± 8°) with no flip of propionate. The energetic cost of the CO-induced Leu-propionate movements is reflected in a 600 mV (57.9 kJmol-1) decrease in haem potential, a value in good agreement with density functional theory calculations. Substitution of Leu by Ala or Gly (structures determined at 1.03 and 1.04 Å resolutions) resulted in a haem site that binds CO in the linear mode only and where no significant change in redox potential is observed. Remarkably, these variants were isolated as ferrous 6c–CO complexes, attributable to the observed eight orders of magnitude increase in affinity for CO, including an approximately 10,000-fold decrease in the rate of dissociation. These new findings have wide implications for preventing CO poisoning of gas-binding haem proteins.