Department of Biology, University of Konstanz, Universitätsstrasse 10, 78457, Konstanz, Germany.
J Biol Inorg Chem. 2022 Feb;27(1):1-21. doi: 10.1007/s00775-021-01921-4. Epub 2021 Dec 5.
Since the characterization of cytochrome c as a multiheme nitrite reductase, research on this enzyme has gained major interest. Today, it is known as pentaheme cytochrome c nitrite reductase (NrfA). Part of the NH produced from NO is released as NH leading to nitrogen loss, similar to denitrification which generates NO, NO, and N. NH can also be used for assimilatory purposes, thus NrfA contributes to nitrogen retention. It catalyses the six-electron reduction of NO to NH, hosting four His/His ligated c-type hemes for electron transfer and one structurally differentiated active site heme. Catalysis occurs at the distal side of a Fe(III) heme c proximally coordinated by lysine of a unique CXXCK motif (Sulfurospirillum deleyianum, Wolinella succinogenes) or, presumably, by the canonical histidine in Campylobacter jejeuni. Replacement of Lys by His in NrfA of W. succinogenes led to a significant loss of enzyme activity. NrfA forms homodimers as shown by high resolution X-ray crystallography, and there exist at least two distinct electron transfer systems to the enzyme. In γ-proteobacteria (Escherichia coli) NrfA is linked to the menaquinol pool in the cytoplasmic membrane through a pentaheme electron carrier (NrfB), in δ- and ε-proteobacteria (S. deleyianum, W. succinogenes), the NrfA dimer interacts with a tetraheme cytochrome c (NrfH). Both form a membrane-associated respiratory complex on the extracellular side of the cytoplasmic membrane to optimize electron transfer efficiency. This minireview traces important steps in understanding the nature of pentaheme cytochrome c nitrite reductases, and discusses their structural and functional features.
自从细胞色素 c 被鉴定为多血红素亚硝酸盐还原酶以来，人们对这种酶的研究产生了浓厚的兴趣。如今，它被称为五血红素细胞色素 c 亚硝酸盐还原酶（NrfA）。部分由 NO 产生的 NH 会作为 NH 释放出来，导致氮的损失，类似于产生 NO、NO 和 N 的反硝化作用。NH 也可用于同化目的，因此 NrfA 有助于氮的保留。它催化 NO 向 NH 的六电子还原，含有四个 His/His 配位的 c 型血红素用于电子转移和一个结构上不同的活性位点血红素。催化作用发生在一个独特的 CXXCK 基序（脱硫螺旋菌、琥珀酸肠杆菌）赖氨酸配位的 Fe(III)血红素 c 的近端，或者推测是 Campylobacter jejeuni 中的典型组氨酸的远端。琥珀酸肠杆菌 NrfA 中的 Lys 被 His 取代会导致酶活性显著丧失。高分辨率 X 射线晶体学表明，NrfA 形成同源二聚体，并且存在至少两种不同的电子转移系统到酶。在 γ-变形菌（大肠杆菌）中，NrfA 通过一个五血红素电子载体（NrfB）与质膜中的menaquinol 池相连，在 δ-和 ε-变形菌（脱硫螺旋菌、琥珀酸肠杆菌）中，NrfA 二聚体与一个四血红素细胞色素 c（NrfH）相互作用。两者在质膜的细胞外侧形成一个与膜相关的呼吸复合物，以优化电子转移效率。这篇综述追溯了理解五血红素细胞色素 c 亚硝酸盐还原酶性质的重要步骤，并讨论了它们的结构和功能特征。
