Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91106, USA.
Metrodora Institute, West Valley City, UT, USA 84119.
Biochim Biophys Acta Bioenerg. 2022 Nov 1;1863(8):148907. doi: 10.1016/j.bbabio.2022.148907. Epub 2022 Aug 6.
The heme‑copper oxidoreductase (HCO) superfamily is a large superfamily of terminal respiratory enzymes that are widely distributed across the three domains of life. The superfamily includes biochemically diverse oxygen reductases and nitric oxide reductases that are pivotal in the pathways of aerobic respiration and denitrification. The adaptation of HCOs to use quinol as the electron donor instead of cytochrome c has significant implication for the respiratory flexibility and energetic efficiency of the respiratory chains that include them. In this work, we explore the adaptation of this scaffold to two different electron donors, cytochromes c and quinols, with extensive sequence analysis of these enzymes from publicly available datasets. Our work shows that quinol oxidation evolved independently within the HCO superfamily at least seven times. Enzymes from only two of these independently evolved clades have been biochemically well-characterized. Combining structural modeling with sequence analysis, we identify putative quinol binding sites in each of the novel quinol oxidases. Our analysis of experimental and modeling data suggests that the quinol binding site appears to have evolved at the same structural position within the scaffold more than once.
血红素铜氧化还原酶（HCO）超家族是一个大型的末端呼吸酶超家族，广泛分布于生命的三个领域。该超家族包括生化多样性的氧还原酶和一氧化氮还原酶，它们在需氧呼吸和反硝化途径中起着关键作用。HCO 适应使用醌作为电子供体而不是细胞色素 c，这对包括它们在内的呼吸链的呼吸灵活性和能量效率具有重要意义。在这项工作中，我们通过对来自公开数据集的这些酶的广泛序列分析，探索了该支架适应两种不同电子供体（细胞色素 c 和醌）的情况。我们的工作表明，醌氧化在 HCO 超家族内至少独立进化了七次。仅来自其中两个独立进化分支的酶已经得到了很好的生化表征。我们将结构建模与序列分析相结合，在每个新的醌氧化酶中确定了可能的醌结合位点。我们对实验和建模数据的分析表明，在支架内的同一结构位置，醌结合位点似乎已经不止一次进化。
