Menaquinone-7 is specific cofactor in tetraheme quinol dehydrogenase CymA.
Menaquinone-7 is specific cofactor in tetraheme quinol dehydrogenase CymA.
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Menaquinone-7 是四血红素醌醇脱氢酶 CymA 的特异性辅因子。
DOI：
10.1074/jbc.m112.348813
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发表时间：
2012-04-20
期刊：
影响因子：
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通讯作者：
Jeuken LJ
中科院分区：
文献类型：
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作者：
McMillan DG;Marritt SJ;Butt JN;Jeuken LJ
背景：CymA是希瓦氏菌无氧呼吸中的中心甲基萘醌-7脱氢酶。结论：CymA具有一个对甲萘醌-7特异性的辅因子位点和一个与醌库平衡的低亲和力Q/QH 2位点。重要性：需要重新评估醌的功能，并且晶体学确定醌结合口袋可能不是醌转化的位点。鲜为人知的是，酶醌-醌醇互变的脂质膜相比，我们的知识底物转化的球状酶。在这里，对自然界中最小的醌醇脱氢酶CymA进行了研究。CymA是一个单调的膜四血红素C型细胞色素属于NapC/NirT家庭和中央希瓦氏菌属无氧呼吸。使用蛋白膜电化学，它表明，囊泡结合甲基萘醌-7不仅是这种酶的底物，但也需要作为辅因子时，转换其他醌。在这里，我们提出，高浓度的醌类在膜上否定了进化的压力，创造一个高亲和力的活性位点。然而，反应中间体半醌的不稳定性和反应性可能需要辅助因子，其功能是使破坏性副反应最小化。
Background: CymA is the central menaquinol-7 dehydrogenase in anaerobic respiration of Shewanella sp. Results: CymA uses menaquinone-7 as a cofactor. Conclusion: CymA has one cofactor site that is specific for menaquinone-7 and one low affinity Q/QH2 site that is in equilibrium with the quinone pool. Significance: The function of quinones needs to be reevaluated and crystallographically determined quinone binding pockets might not be the site of quinone conversion. Little is known about enzymatic quinone-quinol interconversions in the lipid membrane when compared with our knowledge of substrate transformations by globular enzymes. Here, the smallest example of a quinol dehydrogenase in nature, CymA, has been studied. CymA is a monotopic membrane tetraheme c-type cytochrome belonging to the NapC/NirT family and central to anaerobic respiration in Shewanella sp. Using protein-film electrochemistry, it is shown that vesicle-bound menaquinone-7 is not only a substrate for this enzyme but is also required as a cofactor when converting other quinones. Here, we propose that the high concentration of quinones in the membrane negates the evolutionary pressure to create a high affinity active site. However, the instability and reactivity of reaction intermediate, semiquinone, might require a cofactor that functions to minimize damaging side reactions.