+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus

Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus

Biophysical Journal 107(9): 2177-2184

A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

(PDF emailed within 0-6 h: $19.90)

Accession: 055260598

Download citation: RISBibTeXText

PMID: 25418102

DOI: 10.1016/j.bpj.2014.09.010

Related references

Proton transfer in ba(3) cytochrome c oxidase from Thermus thermophilus. Biochimica et Biophysica Acta 1817(4): 650-657, 2012

Timing of electron and proton transfer in the ba(3) cytochrome c oxidase from Thermus thermophilus. Biochemistry 51(22): 4507-4517, 2012

Functional role of Thr-312 and Thr-315 in the proton-transfer pathway in ba3 Cytochrome c oxidase from Thermus thermophilus. Biochemistry 49(33): 7033-7039, 2010

Electrical current generation and proton pumping catalyzed by the ba3-type cytochrome c oxidase from Thermus thermophilus. Febs Letters. 434(1-2): 17-22,. 28, 1998

The cytochrome ba3 oxygen reductase from Thermus thermophilus uses a single input channel for proton delivery to the active site and for proton pumping. Proceedings of the National Academy of Sciences of the United States of America 106(38): 16169-16173, 2009

Electron and proton transfer in the ba(3) oxidase from Thermus thermophilus. Journal of Bioenergetics and Biomembranes 40(4): 281-287, 2008

Conserved glycine 232 in the ligand channel of ba3 cytochrome oxidase from Thermus thermophilus. Biochemistry 53(27): 4467-4475, 2014

A novel c-type cytochrome transfers electrons between sulfite oxidase and cytochrome c552 in the respiratory chain of Thermus thermophilus. Biochimica et Biophysica Acta - Bioenergetics 1797(Supp-S): 22-0, 2010

Single mutations that redirect internal proton transfer in the ba3 oxidase from Thermus thermophilus. Biochemistry 52(40): 7022-7030, 2014

The cytochrome ba3 oxidase from Thermus thermophilus does not generate a tryptophan radical during turnover: Implications for the mechanism of proton pumping. Biochimica et Biophysica Acta 1847(10): 1093-1100, 2015

Toward a chemical mechanism of proton pumping by the B-type cytochrome c oxidases: application of density functional theory to cytochrome ba3 of Thermus thermophilus. Journal of the American Chemical Society 130(45): 15002-15021, 2008

The CuA domain of Thermus thermophilus ba3-type cytochrome c oxidase at 1.6 ANG resolution. Nature Structural Biology 6(6): 509-516, 1999

The Electron Transfer Complex between Cytochrome c and the CuA Domain of the Thermus thermophilus ba Oxidase: A COMBINED NMR AND COMPUTATIONAL APPROACH. Journal of biological chemistry 19 281(20): 14503-14513, 2006

The electron transfer complex between cytochrome c552 and the CuA domain of the Thermus thermophilus ba3 oxidase. A combined NMR and computational approach. Journal of Biological Chemistry 281(20): 14503-14513, 2006

Peculiarities of cyanide binding to the ba3-type cytochrome oxidase from the thermophilic bacterium Thermus thermophilus. Biochemistry. Biokhimiia 75(3): 342-352, 2010