ArticleBiochemistry2010
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.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Structural and functional mechanisms of cytochrome c oxidase.Journal of inorganic biochemistry · 2025Review
- Proton transfer reactions: From photochemistry to biochemistry and bioenergetics.BBA advances · 2023Article
- Snapshot of an oxygen intermediate in the catalytic reaction of cytochromeProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase.The Journal of membrane biology · 2018Article
- Cavity hydration dynamics in cytochromeProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Understanding the essential proton-pumping kinetic gates and decoupling mutations in cytochromeProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural Changes and Proton Transfer in Cytochrome c Oxidase.Scientific reports · 2015Article
- Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.Chemical science · 2015Article
- Conformational coupling between the active site and residues within the K(C)-channel of the Vibrio cholerae cbb3-type (C-family) oxygen reductase.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The K(C) channel in the cbb3-type respiratory oxygen reductase from Rhodobacter capsulatus is required for both chemical and pumped protons.Journal of bacteriology · 2014Article
- Philosophy of voltage-gated proton channels.Journal of the Royal Society, Interface · 2014Review
- Single mutations that redirect internal proton transfer in the ba3 oxidase from Thermus thermophilus.Biochemistry · 2013Article
- Functions of the hydrophilic channels in protonmotive cytochrome c oxidase.Journal of the Royal Society, Interface · 2013Review
- Role of aspartate 132 at the orifice of a proton pathway in cytochrome c oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Product-controlled steady-state kinetics between cytochrome aa(3) from Rhodobacter sphaeroides and equine ferrocytochrome c analyzed by a novel spectrophotometric approach.Biochimica et biophysica acta · 2012Article
- From static structure to living protein: computational analysis of cytochrome c oxidase main-chain flexibility.Biophysical journal · 2012Article
- Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins.Biochimica et biophysica acta · 2012Review
- Alternative initial proton acceptors for the D pathway of Rhodobacter sphaeroides cytochrome c oxidase.Biochemistry · 2011Article
- Crystallographic and online spectral evidence for role of conformational change and conserved water in cytochrome oxidase proton pump.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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4 authors.
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Abstract
The aa(3)-type cytochrome c oxidase from Rhodobacter sphaeroides utilizes two proton-input channels to provide all the protons for chemistry (water formation) and proton pumping. The D-channel is responsible for the uptake of all pumped protons, four protons per O(2). Several substitutions of either N139 or N207, near the entrance of the D-channel, were previously reported to decouple the proton pump from oxidase activity. In this work, the characteristics of additional mutations in this region of the protein (N139, N207, N121, and S142) are determined to elucidate the mechanism of decoupling. With the exception of the substitution of a large, hydrophobic residue (N139L), all the mutations of N139 resulted in an enzyme with high oxidase activity but with a severely diminished proton pumping stoichiometry. Whereas N207D was previously shown to be decoupled, N207A and N207T exhibit nearly wild-type behavior. The new data display a pattern. Small, nonionizable substitutions of N139 or N121 result in decoupling of the proton pump but maintain high turnover rates. These residues are directly hydrogen bonded to two water molecules (Water6574 and Water6584) that are part of the single-file chain of water molecules within the D-channel leading to E286 at the top of the channel. The data suggest that the integrity of this water chain within the D-channel is critical for rapid proton transfer. The mechanism of decoupling is most likely due to the slowing of the rate of proton delivery below a threshold that is required for protonation of the putative proton loading site. Protons delivered outside this time window are delivered to the active site where they are consumed in the formation of water. The rate of proton delivery required to protonate the pump site must be significantly faster than the rate of delivery of protons to the catalytic site. For this reason, mutations can result in decoupling of the proton pump without slowing the catalytic turnover by the enzyme.
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