Structural insights into functional properties of the oxidized form of cytochrome c oxidase
Open Access
- 16 September 2023
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 14 (1) , 1-10
Abstract
Cytochrome c oxidase (CcO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the CcO reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable OH state, and a reductive phase, in which OH is reduced back to the R state. During each phase, two protons are translocated across the membrane. However, if OH is allowed to relax to the resting oxidized state (O), a redox equivalent to OH, its subsequent reduction to R is incapable of driving proton translocation. Here, with resonance Raman spectroscopy and serial femtosecond X-ray crystallography (SFX), we show that the heme a3 iron and CuB in the active site of the O state, like those in the OH state, are coordinated by a hydroxide ion and a water molecule, respectively. However, Y244, critical for the oxygen reduction chemistry, is in the neutral protonated form, which distinguishes O from OH, where Y244 is in the deprotonated tyrosinate form. These structural characteristics of O provide insights into the proton translocation mechanism of CcO.Keywords
Funding Information
- DOE | LDRD | SLAC National Accelerator Laboratory (DE-AC02-76SF00515)
- NSF | Directorate for Mathematical & Physical Sciences | Division of Chemistry (CHE-1404929)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (P41 GM139687, GM126297, GM115773)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (S10 OD023453)
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