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TitleCryo-EM structures of intermediates suggest an alternative catalytic reaction cycle for cytochrome c oxidase.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 6903, Year 2021
Publish dateNov 25, 2021
AuthorsF Kolbe / S Safarian / Ż Piórek / S Welsch / H Müller / H Michel /
PubMed AbstractCytochrome c oxidases are among the most important and fundamental enzymes of life. Integrated into membranes they use four electrons from cytochrome c molecules to reduce molecular oxygen (dioxygen) ...Cytochrome c oxidases are among the most important and fundamental enzymes of life. Integrated into membranes they use four electrons from cytochrome c molecules to reduce molecular oxygen (dioxygen) to water. Their catalytic cycle has been considered to start with the oxidized form. Subsequent electron transfers lead to the E-state, the R-state (which binds oxygen), the P-state (with an already split dioxygen bond), the F-state and the O-state again. Here, we determined structures of up to 1.9 Å resolution of these intermediates by single particle cryo-EM. Our results suggest that in the O-state the active site contains a peroxide dianion and in the P-state possibly an intact dioxygen molecule, the F-state may contain a superoxide anion. Thus, the enzyme's catalytic cycle may have to be turned by 180 degrees.
External linksNat Commun / PubMed:34824221 / PubMed Central
MethodsEM (single particle)
Resolution2.4 - 2.66 Å
Structure data

EMDB-11921, PDB-7ate:
Cytochrome c oxidase structure in P-state
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-11922, PDB-7atn:
Cytochrome c oxidase structure in R-state
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-11924, PDB-7au3:
Cytochrome c oxidase structure in F-state
Method: EM (single particle) / Resolution: 2.56 Å

EMDB-11925, PDB-7au6:
Cytochrome c oxidase structure in O-state
Method: EM (single particle) / Resolution: 2.4 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-HEA:
HEME-A / Heme A

ChemComp-CU:
COPPER (II) ION / Copper

ChemComp-CA:
Unknown entry

ChemComp-PEO:
HYDROGEN PEROXIDE / Hydrogen peroxide

ChemComp-CUA:
DINUCLEAR COPPER ION

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-PGV:
(1R)-2-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL (11E)-OCTADEC-11-ENOATE / phospholipid*YM / Phosphatidylglycerol

ChemComp-HOH:
WATER / Water

ChemComp-O:
OXYGEN ATOM / Oxygen

ChemComp-2FK:
SUPEROXO ION / Superoxide

ChemComp-OXY:
OXYGEN MOLECULE / Oxygen

Source
  • paracoccus denitrificans (bacteria)
KeywordsMEMBRANE PROTEIN / Terminal oxidase Cytochrome c oxidase aa3 oxidase

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