ArticleBiochimica et biophysica acta2011
Exploration of the cytochrome c oxidase pathway puzzle and examination of the origin of elusive mutational effects.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- On the control of the proton current in the voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 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
- Analyzing the electrogenicity of cytochrome c oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Structural Changes and Proton Transfer in Cytochrome c Oxidase.Scientific reports · 2015Article
- Mutation of a single residue in the ba3 oxidase specifically impairs protonation of the pump site.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.Chemical science · 2015Article
- Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochrome c oxidase.Proceedings of the National Academy of Sciences of the United States of America · 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
- Capturing the energetics of water insertion in biological systems: the water flooding approach.Proteins · 2013Article
- Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Expanding the view of proton pumping in cytochrome c oxidase through computer simulation.Biochimica et biophysica acta · 2012Article
- Insights into the mechanism of proton transport in cytochrome c oxidase.Journal of the American Chemical Society · 2012Article
- pH-Dependent conformational changes in proteins and their effect on experimental pK(a)s: the case of Nitrophorin 4.PLoS computational biology · 2012Article
- Electrostatic origin of the mechanochemical rotary mechanism and the catalytic dwell of F1-ATPase.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Proton-transport mechanisms in cytochrome c oxidase revealed by studies of kinetic isotope effects.Biochimica et biophysica acta · 2011Article
- Kinetic design of the respiratory oxidases.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Molecular mechanisms for generating transmembrane proton gradients.Biochimica et biophysica actaReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Gaining detailed understanding of the energetics of the proton-pumping process in cytochrome c oxidase (CcO) is a problem of great current interest. Despite promising mechanistic proposals, so far, a physically consistent model that would reproduce all the relevant barriers needed to create a working pump has not been presented. In addition, there are major problems in elucidating the origin of key mutational effects and in understanding the nature of the apparent pK(a) values associated with the pH dependencies of specific proton transfer (PT) reactions in CcO. This work takes a key step in resolving the above problems, by considering mutations, such as the Asn139Asp replacement, that blocks proton pumping without affecting PT to the catalytic site. We first introduce a formulation that makes it possible to relate the apparent pK(a) of Glu286 to different conformational states of this residue. We then use the new formulation along with the calculated pK(a) values of Glu286 at these different conformations to reproduce the experimentally observed apparent pK(a) of the residue. Next, we take the X-ray structures of the native and Asn139Asp mutant of the Paracoccus denitrificans CcO (N131D in this system) and reproduce for the first time the change in the primary PT pathways (and other key features) based on simulations that start with the observed structural changes. We also consider the competition between proton transport to the catalytic site and the pump site, as a function of the bulk pH, as well as the H/D isotope effect, and use this information to explore the relative height of the two barriers. The paper emphasizes the crucial role of energy-based considerations that include the PT process, and the delicate control of PT in CcO.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.