Evolution of the cytochrome bd oxygen reductase superfamily and the function of CydAA’ in Archaea

Abstract

Cytochrome bd-type oxygen reductases (cytbd) belong to one of three enzyme superfamilies that catalyze oxygen reduction to water. They are widely distributed in Bacteria and Archaea, but the full extent of their biochemical diversity is unknown. Here we used phylogenomics to identify 3 families and several subfamilies within the cytbd superfamily. The core architecture shared by all members of the superfamily consists of four transmembrane helices that bind two active site hemes, which are responsible for oxygen reduction. While previously characterized cytochrome bd-type oxygen reductases use quinol as an electron donor to reduce oxygen, sequence analysis shows that only one of the identified families has a conserved quinol binding site. The other families are missing this feature, suggesting that they use an alternative electron donor. Multiple gene duplication events were identified within the superfamily, resulting in significant evolutionary and structural diversity. The CydAA' cytbd, found exclusively in Archaea, is formed by the co-association of two superfamily paralogs. We heterologously expressed CydAA' from Caldivirga maquilingensis and demonstrated that it performs oxygen reduction with quinol as an electron donor. Strikingly, CydAA' is the first isoform of cytbd containing only b-type hemes shown to be active when isolated, demonstrating that oxygen reductase activity in this superfamily is not dependent on heme d.

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide

“…bd QO is a quinone-type terminal respiratory enzyme that distributes widely in bacteria and archaea. Unlike HCOs that have two hemes and a copper in the active sites, bd QOs accept electrons from quinones (ubiquinol or menaquinol) to reduce oxygen to water using three hemes (Figure 2B) [14,76]. A few isoforms of the bd QO family contain only b-type hemes, which are less sensitive to inhibition by cyanide [77].…”

Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics

“…Cytochrome bd -I and cytochrome bd -II are members of the L subfamily of the cytochrome bd oxygen reductase family [ 127 , 128 ]. According to recent work by Murali et al [ 129 ], the latter family should be expanded into a huge superfamily. The bd oxidase has the UQ8/MQ8 binding site, and three heme prosthetic groups, b 558 , b 595 , and d but lacks any copper site [ 97 , 98 , 108 , 127 , 130 , 131 , 132 , 133 ].…”

Recent Advances in Structural Studies of Cytochrome bd and Its Potential Application as a Drug Target

“…The terminal oxidase cytochrome bd (EC 7.1.1.7) is so far found only in the electron transport chains (also known as the respiratory chains) of bacteria and archaea [ 1 ]. Notably, even some microorganisms considered to be strict anaerobes possess the active bd oxidase to respire, which enhances their growth [ 2 , 3 ].…”

“…Accordingly, it was divided into two subfamilies: L (long Q-loop) and S (short Q-loop) [ 16 , 17 ]. However, very recently the phylogeny of the bd family has been reassessed by Murali et al [ 1 ]. As a result, three families and several subfamilies within the cytochrome bd superfamily have been identified (see [ 1 ] for details).…”

“…However, very recently the phylogeny of the bd family has been reassessed by Murali et al [ 1 ]. As a result, three families and several subfamilies within the cytochrome bd superfamily have been identified (see [ 1 ] for details). Heme d is the site for O 2 binding, usually with a very high affinity, and activation for reduction to 2H 2 O [ 18 , 19 ].…”