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

Abstract

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.

Authors:

Ishigami, Izumi  ^[1];

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Lewis-Ballester, Ariel ^[1]; Echelmeier, Austin ^[2]; Brehm, Gerrit ^[3]; Zatsepin, Nadia A. ^[4]; Grant, Thomas D. ^[5]; Coe, Jesse D. ^[2]; Lisova, Stella ^[2]; Nelson, Garrett ^[4]; Zhang, Shangji ^[2]; Dobson, Zachary F. ^[2]; Boutet, Sébastien ^[6]; Sierra, Raymond G. ^[6]; Batyuk, Alexander  ^[6];

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Fromme, Petra ^[2]; Fromme, Raimund ^[2]; Spence, John C. H. ^[4]; Ros, Alexandra ^[2]; Yeh, Syun-Ru  ^[1];

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Rousseau, Denis L. ^[1]

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+ Show Author Affiliations

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

Publication Date:

2019-02-11

Research Org.:

SLAC National Accelerator Lab., Menlo Park, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:

1494322

Alternate Identifier(s):

OSTI ID: 1506175

Grant/Contract Number:  

AC02-76SF00515; GM098799; GM126297; GM115773; GM095583; CHE-1404929; ABI-1565180; STC-1231306

Resource Type:

Published Article

Journal Name:

Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:

Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 116 Journal Issue: 9; Journal ID: ISSN 0027-8424

Publisher:

Proceedings of the National Academy of Sciences

Country of Publication:

United States

Language:

English

Subject:

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; bioenergetics; complex IV; X-ray free electron laser; crystallography; catalytic intermediates