Redox‐linked conformational changes in cytochrome <i>c</i> oxidase

Wittung, Pernilla; Malmström, Bo G.

doi:10.1016/0014-5793(96)00513-3

Cited by 13 publications

(9 citation statements)

References 19 publications

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“…The structural change between oxidized and reduced cytochrome cd 1 shows how redox energy can be switched into conformational energy within a haem protein, a phenomenon of general importance [25][26][27] . Similar switching occurs in the refolding of mitochondrial cytochrome c, which involves a His-His coordinated haem c on the way to the final His-Met coordinated structure [5][6][7][8] .…”

mentioning

confidence: 99%

Haem-ligand switching during catalysis in crystals of a nitrogen-cycle enzyme

Williams

Fülöp

Garman

et al. 1997

Nature

292

353

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Cytochrome cd1 nitrite reductase catalyses the conversion of nitrite to nitric oxide in the nitrogen cycle. The crystal structure of the oxidized enzyme shows that the d1 haem iron of the active site is ligated by His/Tyr side chains, and the c haem iron is ligated by a His/His ligand pair. Here we show that both haems undergo re-ligation during catalysis. Upon reduction, the tyrosine ligand of the d1 haem is released to allow substrate binding. Concomitantly, a refolding of the cytochrome c domain takes place, resulting in an unexpected change of the c haem iron coordination from His 17/His 69 to Met106/His69. This step is similar to the last steps in the folding of cytochrome c. The changes must affect the redox potential of the haems, and suggest a mechanism by which internal electron transfer is regulated. Structures of reaction intermediates show how nitric oxide is formed and expelled from the active-site iron, as well as how both haems return to their starting coordination. These results show how redox energy can be switched into conformational energy within a haem protein.

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mentioning

confidence: 99%

Haem-ligand switching during catalysis in crystals of a nitrogen-cycle enzyme

Williams

Fülöp

Garman

et al. 1997

Nature

292

353

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“…There is, however, a growing body of evidence that muscle mitochondria are capable of changing their inner membrane potential with concomitant effects on oxidative phosphorylation (6,23,24). This may also effect the enzyme's redox state.…”

Section: Discussionmentioning

confidence: 99%

“…The redox state of cytochrome C oxidase is important to the normal function of the enzyme and there is evidence for conformational changes of the enzyme caused by different redox states (6). Under aerobic conditions, the fully reduced enzyme is not normally found (1) and there is little in vivo data on the relative toxicity responses of the protein in the different redox states.…”

Section: Introductionmentioning

confidence: 99%

Intact smooth muscle metabolism its responses to cyanide poisoning and pyruvate stimulation

Matsumoto²,

Nakayama³

2000

Front Biosci

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Smooth muscle mitochondria are unique in their compartmentalization of metabolism with the contractile proteins and putative role in cell fate choice. In this study we examine the relative and quantitative differences that smooth muscle mitochondria have with regard to cyanide inhibition. The effect of cyanide poisoning in the mitochondria of smooth muscle was examined in the intact porcine carotid artery and intact guinea pig stomach. The respiratory responses of these tissues were monitored in the presence of cyanide and following the addition of various metabolites. In HEPES buffer with 10 mM glucose as the substrate, it was found that the EC 50 for cyanide inhibition was 0.11±0.02 and 0.14±0.02 mM in the pig carotid and guinea stomach respectively. We also found that the signaling metabolite, pyruvate could partially reverse this inhibition. With pyruvate (10 mM) as the substrate, the EC 50 increased significantly to 6.52±0.11 (carotid artery) and 1.95±0.30 (stomach) mM as well as being significantly different between the tissues. This apparent resistance to cyanide inhibition caused by pyruvate was lost when sodium bicarbonate buffer was used (EC 50 in the presence of pyruvate of 0.13±0.04 and 0.25±0.04 for carotid and stomach respectively). HEPES buffer permitted pyruvate's protection from cyanide poisoning whereas bicarbonate buffer did not. The rate of respiration caused by pyruvate re-stimulation was not significantly different than control in the stomach (2.63±0.77 and 2.69±0.3 µMol O 2 /min/g dw respectively) but was significantly greater in the carotid artery. Therefore, smooth muscle with 10 mM pyruvate and 1 mM cyanide had a rate or respiration significantly greater than with 10 mM glucose alone (0.90±0.2 and 0.59±0.06 µMol O 2 /min/g dw respectively). Using 31 P NMR spectroscopy, we observed a complete normalisation of high energy phosphates and pH in the guinea pig stomach smooth muscle caused by pyruvate after cyanide poisoning. These results suggest that cyanide's toxicity of smooth muscle oxidative metabolism is affected by the buffer (HEPES versus Bicarbonate) and metabolic signalling molecules or substrates (pyruvate versus glucose) in which the tissues are exposed to as well as tissue to tissue variations.

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“…Cytochrome c oxidase (CcO) mediates electron transfer from the outside to the inside of the inner mitochondrial membrane, and this transmembrane electron transfer is coupled with the pumping of protons from the inside to the outside of the membrane 1–13. Electrons are supplied by the physiological substrate cytochrome c and are then carried over to the heme a 3 –Cu B binuclear site via a dinuclear copper site (Cu A ) and heme a (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Associated with the dioxygen reaction, protons are also transferred; a part of the protons are carried to the oxygen‐reduction site and are consumed in the chemical reaction while the other protons move across the protein, presumably through a different channel, and generate a transmembrane proton gradient. Several models were proposed to explain the mechanism of coupling of electron transfer to proton translocation in CcO 2, 5–7. The underlying principle of most of the proposed mechanisms is based on some kind of conformational gating that would control the proton flow.…”

Section: Introductionmentioning

confidence: 99%

Redox-linked conformational changes in bovine heart cytochromec oxidase: Picosecond time-resolved fluorescence studies of cyanide complex

Das

Mazumdar

2000

Biopolymers

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Picosecond time‐resolved fluorescence studies are carried out on cyanide‐inhibited and heat‐modified cytochrome c oxidase in aqueous lauryl maltoside surfactant solution, as well as in an aqueous vesicle, to understand the conformational changes associated with electron transfer and proton pumping activity of the enzyme. The tryptophan fluorescence decay profiles follow a four exponential model, which also matches the lifetime maxima obtained in a maximum entropy method analysis. The fast lifetime components are highly affected by the reduction and chemical modification of the enzyme. Changes in these lifetime components are related to the conformational changes in the vicinity of the heme centers of the enzyme. The cyanide‐inhibited enzyme in the oxidized form shows a fluorescence decay profile similar to that of the native oxidized form, indicating that the conformational changes due to cyanide binding are very small. However, reduction of the cyanide‐inhibited enzyme that leaves cyanide bound heme a3 oxidized causes a large increase in the fluorescence lifetimes, which indicates very significant conformational changes due to electron transfer to the dinuclear CuA and heme a centers. A comparison of the tryptophan fluorescence decay of various other modified forms of the enzyme leads us to propose that the possible site of conformational coupling is located near heme a instead of the binuclear heme a3–CuB center. © 2000 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 316–322, 2000

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Redox‐linked conformational changes in cytochrome c oxidase

Abstract: measurements were made at 25°C in potassium phosphate buffers (0.5 mM or, in the experiment illustrated in Fig. 3A, 5 mM), pH 7.5,

Cited by 13 publications

References 19 publications

Haem-ligand switching during catalysis in crystals of a nitrogen-cycle enzyme

Haem-ligand switching during catalysis in crystals of a nitrogen-cycle enzyme

Intact smooth muscle metabolism its responses to cyanide poisoning and pyruvate stimulation

Redox-linked conformational changes in bovine heart cytochromec oxidase: Picosecond time-resolved fluorescence studies of cyanide complex

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