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Title: Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
ORCiD logo [1];  [1];  [2];  [3];  [4];  [5];  [2];  [2];  [4];  [2];  [2];  [6];  [6]; ORCiD logo [6];  [2];  [2];  [4];  [2]; ORCiD logo [1];  [1]
  1. Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461,
  2. Biodesign Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287,, School of Molecular Sciences, Arizona State University, Tempe, AZ 85287,
  3. Biodesign Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287,, School of Molecular Sciences, Arizona State University, Tempe, AZ 85287,, Institute for X-Ray Physics, University of Goettingen, 37077 Goettingen, Germany,
  4. Biodesign Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287,, Department of Physics, Arizona State University, Tempe, AZ 85287,
  5. Hauptman-Woodward Institute and SUNY University of Buffalo, Buffalo, NY 14203,
  6. SLAC National Accelerator Laboratory, Menlo Park, CA 94025

Cytochrome c oxidase (C c O) reduces dioxygen to water and harnesses the chemical energy to drive proton translocation across the inner mitochondrial membrane by an unresolved mechanism. By using time-resolved serial femtosecond crystallography, we identified a key oxygen intermediate of bovine C c O. It is assigned to the P R -intermediate, which is characterized by specific redox states of the metal centers and a distinct protein conformation. The heme a 3 iron atom is in a ferryl (Fe 4+ = O 2− ) configuration, and heme a and Cu B are oxidized while Cu A is reduced. A Helix-X segment is poised in an open conformational state; the heme a farnesyl sidechain is H-bonded to S382, and loop-I-II adopts a distinct structure. These data offer insights into the mechanism by which the oxygen chemistry is coupled to unidirectional proton translocation.

Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1494322
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 9 Vol. 116; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English

References (40)

Proton uptake by cytochrome c oxidase on reduction and on ligand binding journal June 1994
The chemistry of the CuB site in cytochrome c oxidase and the importance of its unique His–Tyr bond journal April 2009
High resolution crystal structure of Paracoccus denitrificans cytochrome c oxidase: New insights into the active site and the proton transfer pathways journal June 2009
Molecular dynamics simulation of water in cytochrome c oxidase reveals two water exit pathways and the mechanism of transport journal September 2009
Functional Hydration and Conformational Gating of Proton Uptake in Cytochrome c Oxidase journal April 2009
Oxygen Activation and Energy Conservation by Cytochrome c Oxidase journal January 2018
Reaction of hydrogen peroxide with the rapid form of resting cytochrome oxidase journal June 1991
Electron transfer between cytochrome a and copper A in cytochrome c oxidase: a perturbed equilibrium study journal August 1989
Role of the P R Intermediate in the Reaction of Cytochrome c Oxidase with O 2 journal June 2001
Decoupling Mutations in the D-Channel of the aa 3 -Type Cytochrome c Oxidase from Rhodobacter sphaeroides Suggest That a Continuous Hydrogen-Bonded Chain of Waters Is Essential for Proton Pumping journal June 2010
Redox-Dependent Conformational Changes in Cytochrome c Oxidase Suggest a Gating Mechanism for Proton Uptake journal June 2009
Proton-Coupled Electron Transfer in Cytochrome Oxidase journal December 2010
Reaction Mechanism of Cytochrome c Oxidase journal January 2015
Proton translocation by cytochrome c oxidase journal July 1999
Femtosecond X-ray protein nanocrystallography journal February 2011
Determination of damage-free crystal structure of an X-ray–sensitive protein using an XFEL journal May 2014
Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase journal October 2016
Structural enzymology using X-ray free electron lasers journal December 2016
The proton pumping pathway of bovine heart cytochrome c oxidase journal February 2007
Glutamic acid 242 is a valve in the proton pump of cytochrome c oxidase journal April 2008
The proton donor for OO bond scission by cytochrome c oxidase journal July 2008
Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature journal July 2017
Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations journal November 2017
The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process journal December 2003
The roles of the two proton input channels in cytochrome c oxidase from Rhodobacter sphaeroides probed by the effects of site-directed mutations on time-resolved electrogenic intraprotein proton transfer journal August 1997
Time Dependence of the Catalytic Intermediates in Cytochrome c Oxidase journal January 2000
Exposure of Bovine Cytochrome c Oxidase to High Triton X-100 or to Alkaline Conditions Causes a Dramatic Change in the Rate of Reduction of Compound F journal July 2001
Effective Pumping Proton Collection Facilitated by a Copper Site (Cu B ) of Bovine Heart Cytochrome c Oxidase, Revealed by a Newly Developed Time-resolved Infrared System journal August 2013
The Mg 2+ -containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle journal September 2016
Kinetic Resolution of a Tryptophan-radical Intermediate in the Reaction Cycle of Paracoccus denitrificans Cytochrome c Oxidase journal August 2007
The Protonation State of the Cross-linked Tyrosine during the Catalytic Cycle of Cytochrome c Oxidase journal October 2008
X-ray structural analyses of azide-bound cytochrome c oxidases reveal that the H-pathway is critically important for the proton-pumping activity journal August 2018
Molecular Mechanism of Proton Translocation by Cytochrome c Oxidase journal January 2008
Functions of the hydrophilic channels in protonmotive cytochrome c oxidase journal September 2013
Polder maps: improving OMIT maps by excluding bulk solvent journal February 2017
The mechanism of coupling between oxido-reduction and proton translocation in respiratory chain enzymes: Protonmotive respiratory chains journal June 2017
A nanosecond time-resolved XFEL analysis of structural changes associated with CO release from cytochrome c oxidase journal July 2017
High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography journal May 2012
Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography journal January 2013
Redox-Controlled Proton Gating in Bovine Cytochrome c Oxidase journal May 2013

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