The Unusual Homodimer of a Heme‐Copper Terminal Oxidase Allows Itself to Utilize Two Electron Donors

Abstract

The heme-copper oxidase superfamily comprises cytochrome cand ubiquinol oxidases.These enzymes catalyze the transfer of electrons from different electron donors onto molecular oxygen. AB-family cytochrome coxidase from the hyperthermophilic bacterium Aquifex aeolicus was discovered previously to be able to use both cytochrome ca nd naphthoquinol as electron donors.Its molecular mechanism as well as the evolutionary significance are yet unknown. Here we solved its 3.4 resolution electron cryo-microscopic structure and discovered an ovel dimeric structure mediated by subunit I (CoxA2) that would be essential for naphthoquinol binding and oxidation. The unique structural features in both proton and oxygen pathways suggest an evolutionary adaptation of this oxidase to its hyperthermophilic environment. Our results add anew conceptual understanding of structural variation of cytochrome co xidases in different species.

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

“…The divalent cations (Mg 2+ or Mn 2+ ) located at the interface between SU-I B-family HCOs comprise similar subunit compositions but with low sequence homology to their A-family counterparts (Figure 2A). In contrast to the canonical composition of 12 TMHs in SU-I of A-family HCOs, SU-Is of B-family HCOs, as seen in CcOs from Thermus thermophilus and Aquifex aeolicus, possess 13 and 14 TMHs, respectively [54,55]. The SU-II of B-family HCOs resembles its A-family counterpart in that both contain a membraneanchored cupredoxin domain; however, an additional subunit (SU-IIa) consisting of a single helix is identified in the former [55].…”

“…In contrast to the canonical composition of 12 TMHs in SU-I of A-family HCOs, SU-Is of B-family HCOs, as seen in CcOs from Thermus thermophilus and Aquifex aeolicus, possess 13 and 14 TMHs, respectively [54,55]. The SU-II of B-family HCOs resembles its A-family counterpart in that both contain a membraneanchored cupredoxin domain; however, an additional subunit (SU-IIa) consisting of a single helix is identified in the former [55]. The His-Tyr cross-link in A-family HCOs, which functions to fix Cu B in a certain configuration and distance from heme a 3 at the BNC [56], is also conserved in B-family HCOs.…”

A Bioinspired Copper-Pair Catalyst in Metal–Organic Frameworks for Molecular Dioxygen Activation and Aerobic Oxidative C–N Coupling

“…Living organisms use metalloenzymes to catalyze various biochemical reactions so as to maintain the good and orderly operation of the organism. , As an important class of metalloenzymes, oxidases effectively activate dioxygen molecules and promote oxidative respiration . Owing to the involvement of multiple metal sites that facilitate multi-electron transfer and spin transition, binuclear or trinuclear Cu centers are a major class of cofactors that bind and activate O 2 in many oxidases including cytochrome c oxidase, − tyrosinase, − catechol oxidase, − laccase, − etc. It has been long of interest mimicking the function of these oxidases in an artificial system and promoting aerobic oxygen utilization in organic reactions, − yet many of these artificial enzymes only exhibited limited activity and reaction/substrate scope so far.…”

Introducing the role of metals in biology to high school and undergraduate students

“…[1][2][3] In fact, it has been estimated that nearly half of all enzymes utilize metals to enable their structural integrity and functional role. [4][5][6][7] For instance, the heme-copper complex in cytochrome c oxidase binds molecular oxygen and facilitates four-electron reduction of oxygen to water during respiration [8][9][10][11][12] (Figure 1A top panel) and the heme-iron cofactor in myoglobin/hemoglobin proteins enables transfer and storage of oxygen (Figure 1A bottom panel). [13][14][15] Similarly, plants use calcium and manganese cofactors to catalyze the oxidation of water during photosynthesis (Figure 1B top panel) 16,17 Metal cofactors critical in biological processes in plants.…”