Flavin Binding to the Deca-heme Cytochrome MtrC: Insights from Computational Molecular Simulation.
Flavin Binding to the Deca-heme Cytochrome MtrC: Insights from Computational Molecular Simulation.
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DOI：
10.1016/j.bpj.2015.10.038
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发表时间：
2015-12-15
影响因子：
3.4
通讯作者：
Blumberger J
中科院分区：
文献类型：
--
作者：
Breuer M;Rosso KM;Blumberger J
某些异化细菌具有使用细胞外金属氧化物矿物质而不是氧气作为末端电子下沉的显着能力，使用称为“细胞外呼吸”的过程。位于微生物外膜上的专门的多血红素细胞色素被证明是电子从细胞表面转移到矿物质的关键。这一过程由生物体分泌的可溶性生物源黄素促进，目的是充当电子穿梭器。然而，它们与外膜细胞色素的相互作用没有在分子尺度上建立。在这里，我们研究了外膜十血红素细胞色素MtrC从希瓦氏菌oneidensis和黄素montobenzide（FMN在完全氧化醌形式）之间的相互作用，使用计算对接。我们发现FMN与MtrC的相互作用明显弱于已知的FMN结合蛋白，但确定了一个接近血红素2的温和首选相互作用位点，解离常数（Kd）= 490 μM，与最近的实验估计值（Kd = 255 μM）非常一致。与MtrC的弱相互作用可以定性地解释为与FMN结合蛋白相比，FMN的平面头基可以与该蛋白形成的氢键数量较少。分子动力学模拟给出了一个可能的构象开关后，裂解的二硫键的MTRC的迹象，但没有随之而来的结合亲和力增加，根据这个对接研究。总体而言，我们的研究结果表明，FMN与MtrC的结合是可逆的，并且不是高度特异性的，这可能与促进细胞外呼吸的氧化还原穿梭的作用一致。
Certain dissimilatory bacteria have the remarkable ability to use extracellular metal oxide minerals instead of oxygen as terminal electron sinks, using a process known as “extracellular respiration”. Specialized multiheme cytochromes located on the outer membrane of the microbe were shown to be crucial for electron transfer from the cell surface to the mineral. This process is facilitated by soluble, biogenic flavins secreted by the organism for the purpose of acting as an electron shuttle. However, their interactions with the outer-membrane cytochromes are not established on a molecular scale. Here, we study the interaction between the outer-membrane deca-heme cytochrome MtrC from Shewanella oneidensis and flavin mononucleotide (FMN in fully oxidized quinone form) using computational docking. We find that interaction of FMN with MtrC is significantly weaker than with known FMN-binding proteins, but identify a mildly preferred interaction site close to heme 2 with a dissociation constant (Kd) = 490 μM, in good agreement with recent experimental estimates, Kd = 255 μM. The weak interaction with MtrC can be qualitatively explained by the smaller number of hydrogen bonds that the planar headgroup of FMN can form with this protein compared to FMN-binding proteins. Molecular dynamics simulation gives indications for a possible conformational switch upon cleavage of the disulphide bond of MtrC, but without concomitant increase in binding affinities according to this docking study. Overall, our results suggest that binding of FMN to MtrC is reversible and not highly specific, which may be consistent with a role as redox shuttle that facilitates extracellular respiration.