首页> 外文期刊>Journal of Molecular Biology >Quinol oxidation by c-type cytochromes: structural characterization of the menaquinol binding site of NrfHA.
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Quinol oxidation by c-type cytochromes: structural characterization of the menaquinol binding site of NrfHA.

机译:C型细胞色素对喹诺醇的氧化作用:NrfHA的薄荷醇结合位点的结构表征。

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Membrane-bound cytochrome c quinol dehydrogenases play a crucial role in bacterial respiration by oxidizing menaquinol and transferring electrons to various periplasmic oxidoreductases. In this work, the menaquinol oxidation site of NrfH was characterized by the determination of the X-ray structure of Desulfovibrio vulgaris NrfHA nitrite reductase complex bound to 2-heptyl-4-hydroxyquinoline-N-oxide, which is shown to act as a competitive inhibitor of NrfH quinol oxidation activity. The structure, at 2.8-A resolution, reveals that the inhibitor binds close to NrfH heme 1, where it establishes polar contacts with two essential residues: Asp89, the residue occupying the heme distal ligand position, and Lys82, a strictly conserved residue. The menaquinol binding cavity is largely polar and has a wide opening to the protein surface. Coarse-grained molecular dynamics simulations suggest that the quinol binding site of NrfH and several other respiratory enzymes lie in the head group region of the membrane, which probably facilitates proton transfer to the periplasm. Although NrfH is not a multi-span membrane protein, its quinol binding site has several characteristics similar to those of quinone binding sites previously described. The data presented here provide the first characterization of the quinol binding site of the cytochrome c quinol dehydrogenase family.
机译:膜结合的细胞色素C喹诺醇脱氢酶通过氧化薄荷醇并将电子转移到各种周质氧化还原酶中,在细菌呼吸中起关键作用。在这项工作中,NrfH的甲萘醌氧化位点的特征是通过测定与2-庚基-4-羟基喹啉-N-氧化物结合的寻常脱硫脱硫弧菌NrfHA亚硝酸还原酶复合物的X射线结构来表征NrfH喹诺酮氧化活性的抑制剂。该结构以2.8-A的分辨率显示,该抑制剂与NrfH血红素1紧密结合,在该处与两个基本残基建立极性接触:Asp89(该残基占据血红素远端配体位置)和Lys82(一个严格保守的残基)。甲萘醌结合腔在很大程度上是极性的,并且对蛋白质表面具有宽阔的开口。粗粒度的分子动力学模拟表明,NrfH和其他几种呼吸酶的喹诺酚结合位点位于膜的头基区域,这可能有助于质子转移至周质。尽管NrfH不是多跨膜蛋白,但其喹诺酚结合位点具有与先前所述的醌结合位点相似的几个特征。此处提供的数据提供了细胞色素C喹诺醇脱氢酶家族的奎诺尔结合位点的第一个特征。

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