Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial cytochrome c oxidase and its bacterial homologs catalyze electron transfer and proton translocation reactions across membranes. The eukaryotic enzyme complex consists of a large number of polypeptide subunits. Three of the subunits (I, II, and III) are mitochondrially encoded while the remaining 6 (yeast) to 10 (bovine) are nuclear encoded. Antibody and chemical-labelling experiments suggest that subunits I-III and most (but not all) of the nuclear-encoded subunits span the inner mitochondrial membrane. Subunits I and II are the catalytic core of the enzyme. Subunit I contains haem a, haem a3 and CuB, while subunit II contains CuA and the cytochrome c binding site. Subunit III and most of the nuclear subunits are essential for the assembly of a functional catalytic enzyme. Some nuclear subunits are present as isozymes, although little functional difference has yet been detected between enzyme complexes composed of different isozymes. Therefore, any additional role attributed to the nuclear-encoded subunits beyond that of enzyme assembly must be tentative. We suggest that enough evidence exists to support the idea that modification of the larger nuclear subunits (IV, V, and possibly VI) can effect enzyme turnover in vitro. Whether this is a physiological control mechanism remains to be seen.
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PMID:Cytochrome c oxidase: structure, function, and membrane topology of the polypeptide subunits. 166 35

The smallest subunit of bovine cytochrome c oxidase (CIX or VIII in different nomenclatures) occurs in two isoforms, a heart (H) form and a liver (L) form. The cDNAs for both of these forms have been isolated and sequenced. The cDNA for the H form encodes a protein 70 amino acids long with a 24-residue presequence and a mature polypeptide of 46 amino acids; that of liver encodes a protein of 69 amino acids, a 25-residue presequence and a mature polypeptide of 44 amino acids. The leader sequences of the H and L forms are 40% homologous with an abundance of positively charged residues but no negatively charged amino acids. These features are typical of polypeptides targeted to the mitochondrion for processing in the matrix space. The homology of the two isoforms is 52% in the mature subunit with most of the differences occurring in the N-terminal hydrophilic domain of the protein. Evidence has been obtained of polymorphisms of both the H and L forms of the subunit. Protein chemical analyses show that the H isoform is the predominant if not the exclusive form of subunit CIX in heart and skeletal muscle tissue. The L form is the predominant form in liver, kidney, and brain. Northern analyses, using cDNAs to the two forms to screen whole cell RNA preparations, show that the transcript of the H isoform is present in heart and skeletal muscle but not in other tissues examined. The mRNA of the L form was found in brain, kidney, and liver and also in heart and skeletal muscle. These results indicate that the synthesis of the H isoform of CIX is controlled transcriptionally while the L form is under post-transcriptional regulation at least in heart and muscle tissue.
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PMID:Isolation and characterization of the cDNAs encoding two isoforms of subunit CIX of bovine cytochrome c oxidase. 168 92

Purified ubiquinol-cytochrome c reductase of beef heart mitochondria is very stable in aqueous solution; it suffers little damage upon illumination with visible light under aerobic or anaerobic conditions. However, it is rapidly inactivated when the photosensitizer hematoporphyrin is present during illumination. The hematoporphyrin-promoted photoactivation is dependent on sensitizer dose, illumination time, and oxygen. Singlet oxygen is shown to be the destructive agent in this system. The photoinactivation of ubiquinol-cytochrome c reductase is prevented by excess exogenous ubiquinone, regardless of its redox state. This protective effect is not due to protein-ubiquinone interactions but to the singlet oxygen scavenger property of ubiquinone. Ubiquinone also protects against hematoporphyrin-promoted photoinactivation of succinate-ubiquinone reductase and cytochrome c oxidase. The photoinactivation site in ubiquinol-cytochrome c reductase is the iron-sulfur cluster of Rieske's protein. Two histidine residues, presumably serving as two ligands for the iron-sulfur cluster of Rieske's protein, are destroyed. No polypeptide bond cleavage is detected. Photoinactivation has little effect on the spectral properties of cytochromes b and c1 but alters their reduction rates substantially. this photoinactivation also causes the formation of proton-leaking channels in the complex. When the photoinactivated reductase is co-inlaid with intact ubiquinol-cytochrome c reductase or cytochrome c oxidase in a phospholipid vesicle, no proton ejection can be detected during the oxidation of their corresponding substrates.
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PMID:Hematoporphyrin-promoted photoinactivation of mitochondrial ubiquinol-cytochrome c reductase: selective destruction of the histidine ligands of the iron-sulfur cluster and protective effect of ubiquinone. 184 89

The two smallest polypeptide components of D. discoideum cytochrome c oxidase, whose alternative expression depends on oxygen concentration [Schiavo, G. and Bisson, R. (1989) J. Biol. Chem. 264, 7129-7134], have been partially sequenced. They show 45% homology and are isoforms of the same subunit, which must be encoded on two different genes.
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PMID:The two oxygen-regulated subunits of cytochrome c oxidase in Dictyostelium discoideum derive from a common ancestor. 215 32

Subunit VIIa of yeast cytochrome c oxidase is a small (59 amino acids) protein of the inner mitochondrial membrane that lacks a cleavable amino-terminal presequence. To identify regions within this polypeptide that are essential for its import, gene fusions were constructed using a leader peptide substitution vector (pLPS) developed in this laboratory (Glaser, S. M., Trueblood, C. E., Dircks, L. K., Poyton, R. O., and Cumsky, M. G. (1988) J. Cell. Biochem. 36, 275-287). In this vector, oligonucleotide sequences encoding all or part of subunit VIIa were fused in-frame with the coding region of mature cytochrome c oxidase subunit Va. The plasmid pLPS is ideal for assaying protein sequences for their ability to direct mitochondrial import in vivo since subunit Va's leader peptide is essential for import and because subunit V is required for cytochrome c oxidase activity and respiration. Strains containing these fusions but lacking both subunit V genes (COX5a and COX5b) were analyzed to determine whether the chimeric protein is directed to mitochondria. Our findings indicate that the amino-terminal 17 amino acids of subunit VIIa are sufficient to localize subunit Va to the mitochondrion and that a 6-amino acid-long region within the amino terminus (Gly8-Arg13) is essential. In addition, some import (approximately 10% of wild type) is observed with the highly charged carboxyl terminus of subunit VIIa, suggesting that the subunit may contain redundancy in its import information.
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PMID:Mitochondrial import of cytochrome c oxidase subunit VIIa in Saccharomyces cerevisiae. Identification of sequences required for mitochondrial localization in vivo. 215 98

The general structure of the enzyme, its polypeptide composition, and a proposal for a rational nomenclature are discussed. The mitochondrially coded and bacterial cytochrome c oxidase subunits have been analyzed with more attention focused on elucidating the number of metals present in the enzyme and the ligands available for their coordination. The picture of a 2 Cu/2 Fe enzyme has been compared with that of a 3 Cu/2 Fe enzyme and a new model is proposed for the location of the metal centers in the enzyme.
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PMID:Cytochrome c oxidases: polypeptide composition, role of subunits, and location of active metal centers. 216 54

We have isolated a full-length human liver cDNA clone specifying the nuclear-encoded subunit IV of the human mitochondrial respiratory chain enzyme, cytochrome c oxidase (COX; EC 1.9.3.1). The human cDNA clone is highly homologous to its bovine counterpart in the coding regions for both the mature polypeptide and the presequence, and the gene is evolving more slowly than that of any of the three mitochondrially encoded COX subunit genes. We find no preliminary evidence for tissue-specific isoforms of COX subunit IV, as Northern analysis of muscle, liver, and HeLa cell RNA shows an identically sized transcript in each cell type.
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PMID:Isolation of a cDNA clone encoding subunit IV of human cytochrome c oxidase. 244 97

The conditions that promote the alternative expression of two nuclear-encoded subunits of cytochrome c oxidase in the slime mold Dictyostelium discoideum (Bisson, R., and Schiavo, G. (1986) J. Biol. Chem. 261, 4373-4376) have been investigated. Oxygen concentration seems to be the only factor able to cause the subunit switching. This result indicates that the polypeptide composition of the mitochondrial enzyme can be influenced by environmental conditions. The significance of this change is discussed.
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PMID:Oxygen influences the subunit structure of cytochrome c oxidase in the slime mold Dictyostelium discoideum. 254 Jan 75

Binding to cytochrome c oxidase induces a conformational change in the cytochrome c molecule. This conformational change has been characterized by comparing the binding of native cytochrome c and chemically modified cytochrome c derivatives to bovine cytochrome c oxidase by using absorption, circular dichroism (CD), and magnetic circular dichroism (MCD) spectroscopy. The following derivatives were analyzed: (i) cytochrome c modified at all 19 lysine residues to yield the (N epsilon-acetimidyl)19 cytochrome c, (N epsilon-isopropyl)19 cytochrome c, and (N epsilon,N epsilon-dimethyl)19 cytochrome c; (ii) cytochrome c in which Met65 and Met80 are converted to the methionine sulfoxide; (iii) cytochrome c with a single break in the polypeptide chain at Arg38 or Gly37. The derivatives bind to cytochrome c oxidase at a ratio of one heme c per heme aa3. The association constants are similar to that of native cytochrome c except for (N epsilon-isopropyl)19 and (N epsilon,N epsilon-dimethyl)19 cytochromes c, which bind respectively four times and six times less strongly. The derivatives are good substrates for the cytochrome c oxidase reaction. The spectral changes accompanying the binding of the modified cytochromes c to cytochrome c oxidase are quite different from the spectral changes observed with native cytochrome c. The different optical absorption and MCD changes are explained by a polarity change around the exposed heme edge in the cytochrome c-cytochrome c oxidase complex. The CD changes indicate a conformational rearrangement restricted to the surface area surrounding the exposed heme edge. The rearrangement may involve a movement of the evolutionarily conserved Phe82 out of the vicinity of the heme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cytochrome c oxidase-cytochrome c complex: spectroscopic analysis of conformational changes in the protein-protein interaction domain. 254 Jul 99

An a-type cytochrome was purified from Halobacterium halobium. The cytochrome showed an absorption spectrum similar to that of cytochrome aa3; it showed absorption peaks at 420 and 598 nm in the resting state, peaks at 441 and 602 nm in the reduced form, and its CO compound showed peaks at 430 and 600 nm. The cytochrome molecule was composed of only one kind of polypeptide with the molecular weight of 40,000. The cytochrome contained two heme a molecules in the molecule but no copper. The cytochrome did not show cytochrome c oxidase activity. Midpoint redox potential at pH 8.0 of the cytochrome was determined to be +0.31 V. The amino acid composition of the cytochrome resembled that of subunit I of mitochondrial cytochrome aa3. While two molecules of heme a were reduced with sodium dithionite, only one of two heme a molecules was reduced with ascorbate plus TMPD. The heme a reduced with ascorbate plus TMPD did not react with molecular oxygen or carbon monoxide, while one of two heme a molecules reduced with sodium dithionite was oxidized by molecular oxygen and combined with carbon monoxide.
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PMID:Purification and properties of Halobacterium halobium "cytochrome aa3" which lacks CuA and CuB. 254 39


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