Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subunit c is normally present as an inner mitochondrial membrane component of the F0 section of the ATP synthase complex, but in the late infantile form of neuronal ceroid lipofuscinosis (NCL) it was also found in lysosomes in high concentrations. To explore the mechanism of storage of subunit c, the rates of degradation and synthesis of subunit c were measured in fibroblast cell types from controls and patients with the late infantile form of NCL. The radiolabel from subunit c decreased with time in control cells, whereas no apparent loss of radioactivity of subunit c was found in patients' cells. There were no significant differences between control cells and cells with disease in the degradation of cytochrome oxidase subunit IV, an inner membrane protein of mitochondria. A combination of pulse-chase and subcellular fractionation analysis showed that a delay of intramitochondrial loss from prelabeled subunit c was seen in all diseased cells tested. Lysosomal appearance of labeled subunit c could be detected after chase for more than 1 week and its radioactivities were variable among diseased cell types. The biosynthetic rate of subunit c was almost the same in both control and patient cells. Northern blotting analyses showed that mRNAs for P1 and P2 genes had no significant difference in lengths and amounts between control and patient cells. Results suggest a specific failure in the degradation of subunit c after its normal inclusion in mitochondria and its consequent accumulation in lysosomes. This is the first direct evidence to show a delay of subunit c degradation in the cells from the late infantile form of NCL.
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PMID:Specific delay of degradation of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid lipofuscinosis (Batten disease). 783 67

While a considerable amount of literature deals with the structural energetics of water-soluble proteins, relatively little is known about the forces that determine the stability of membrane proteins. Similarly, only a few membrane protein structures are known at atomic resolution, although new structures have recently been described. In this article, we review the current knowledge about the structural features of membrane proteins. We then proceed to summarize the existing literature regarding the thermal stability of bacteriorhodopsin, cytochrome-c oxidase, the band 3 protein, Photosystem II and porins. We conclude that a fundamental difference between soluble and membrane proteins is the high thermal stability of intrabilayer secondary structure elements in membrane proteins. This property manifests itself as incomplete unfolding, and is reflected in the observed low enthalpies of denaturation of most membrane proteins. By contrast, the extramembranous parts of membrane proteins may behave much like soluble proteins. A brief general account of thermodynamics factors that contribute to the stability of water soluble and membrane proteins is presented.
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PMID:Forces and factors that contribute to the structural stability of membrane proteins. 764 Feb 99

The genes for a new type of a haem-copper cytochrome oxidase were cloned from Rhodobacter capsulatus strain 37b4, using the Bradyrhizobium japonicum fixNOQP gene region as a hybridizing probe. Four genes, probably organized in an operon (ccoNOQP), were identified; their products share extensive amino acid sequence similarity with the FixN, O, Q and P proteins that have recently been shown to be the subunits of a cb-type oxidase. CcoN is a b-type cytochrome, CcoO and CcoP are membrane-bound mono- and dihaem c-type cytochromes and CcoQ is a small membrane protein of unknown function. Genes for a similar oxidase are also present in other non-rhizobial bacterial species such as Azotobacter vinelandii, Agrobacterium tumefaciens and Pseudomonas aeruginosa, as revealed by polymerase chain reaction analysis. A ccoN mutant was constructed whose phenotype, in combination with the structural information on the gene products, provides evidence that the CcoNOQP oxidase is a cytochrome c oxidase of the cb type, which supports aerobic respiration in R. capsulatus and which is probably identical to the cbb3-type oxidase that was recently purified from a different strain of the same species. Mutant analysis also showed that this oxidase has no influence on photosynthetic growth and nitrogen-fixation activity.
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PMID:The ccoNOQP gene cluster codes for a cb-type cytochrome oxidase that functions in aerobic respiration of Rhodobacter capsulatus. 789 58

Cytochrome c oxidase was isolated from beef heart mitochondria by detergent extraction yielding two different crystal forms. Extraction with Triton detergents produced vesicular crystals with two-dimensional crystalline arrays of cytochrome c oxidase dimers while extraction with sodium deoxycholate produced crystalline sheets of cytochrome c oxidase monomers. The structures of both crystal forms were determined in two-dimensional projection along an axis normal to the plane of the membrane by cryoelectron microscopy of crystals embedded in vitreous ice (frozen-hydrated). The projection structures of unstained frozen hydrated monomers and of dimers are similar to the structures of the crystals in negative stain. The molecular outline of dimers can be approximated by a parallelogram 44 A by 82 A with an included angle of 80 degrees. Monomers are less regular consisting of two large domains with a smaller domain at one end and a total length of approximately 82 A. Comparison of the two structures reveals the orientation of cytochrome c oxidase monomers within dimers, an orientation which is different from earlier models of monomer-monomer interaction, and suggests a very close interaction between monomers when they associate to form dimers. The crystalline sheets of cytochrome c oxidase monomers bind tightly the small peripheral membrane protein substrate, cytochrome c, and this binding accentuates a tendency of these crystals to stack upon one another. Images of crystals of the cytochrome c oxidase/cytochrome c complex were analyzed by crosscorrelation analysis versus the monomer crystal image. Two types of two-layer crystals have been identified. Both types have one layer rotated by 180 degrees with respect to the other, but they differ in the shifts of origin along crystal axes of the two layers. Difference images formed by subtracting simulated multilayered crystal images (which have no bound cytochrome c) from the complex crystals (cytochrome c oxidase plus cytochrome c) contain one positive difference peak for each cytochrome oxidase monomer within a unit cell. Comparison of the difference peak loci among the different crystal forms is interpreted based upon a consensus cytochrome c binding site in the single layer cytochrome oxidase monomer crystal image.
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PMID:Electron microscopy of cytochrome c oxidase crystals. Monomer-dimer relationship and cytochrome c binding site. 814 42

Cytochrome oxidase is a membrane protein complex that catalyzes reduction of molecular oxygen to water and utilizes the free energy of this reaction to generate a transmembrane proton gradient during respiration. The electron entry site in subunit II is a mixed-valence dinuclear copper center in enzymes that oxidize cytochrome c. This center has been lost during the evolution of the quinoloxidizing branch of cytochrome oxidases but can be restored by engineering. Herein we describe the crystal structures of the periplasmic fragment from the wild-type subunit II (CyoA) of Escherichia coli quinol oxidase at 2.5-A resolution and of the mutant with the engineered dinuclear copper center (purple CyoA) at 2.3-A resolution. CyoA is folded as an 11-stranded mostly antiparallel beta-sandwich followed by three alpha-helices. The dinuclear copper center is located at the loops between strands beta 5-beta 6 and beta 9-beta 10. The two coppers are at a 2.5-A distance and symmetrically coordinated to the main ligands that are two bridging cysteines and two terminal histidines. The residues that are distinct in cytochrome c and quinol oxidases are around the dinuclear copper center. Structural comparison suggests a common ancestry for subunit II of cytochrome oxidase and blue copper-binding proteins.
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PMID:Crystal structure of the membrane-exposed domain from a respiratory quinol oxidase complex with an engineered dinuclear copper center. 861 20

C129/U1 is a respiratory defective mutant of Saccharomyces cerevisiae arrested in cytochrome oxidase assembly due to a mutation in COX17, a nuclear gene encoding a low molecular weight cytoplasmic protein proposed to function in mitochondrial copper recruitment. In the present study we show that the respiratory defect of C129/U1 is rescuable by two multicopy suppressors, SCO1 and SCO2. SCO1 was earlier reported to code for a mitochondrial inner membrane protein with an essential function in cytochrome oxidase assembly (Buchwald, P., Krummeck, G., and Rodel, G. (1991) Mol. Gen. Genet. 229, 413-420). SCO2 is a homologue of SCO1, whose product is also localized in the mitochondrial membrane but is not required for respiration. SCO1 also suppresses a cox17 null mutant, indicating that overexpression of Sco1p can compensate for the absence of Cox17p. In contrast, neither copper, COX17 on a multicopy plasmid, or a combination of the two is able to restore respiration in sco1 mutants. Rescue of cox17 mutants by Sco1p suggests that this mitochondrial protein plays a role either in mitochondrial copper transport or insertion of copper into the active site of cytochrome oxidase. Although SCO2 can also partially restore respiratory growth in the cox17 null mutant, rescue in this case requires addition of copper to the growth medium. SCO2 does not suppress a sco1 null mutant, although it is able to partially rescue a sco1 point mutant. We interpret the ability of SCO2 to restore respiration in cox17, but not in sco1 mutants, to indicate that Sco1p and Sco2p have overlapping but not identical functions.
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PMID:SCO1 and SCO2 act as high copy suppressors of a mitochondrial copper recruitment defect in Saccharomyces cerevisiae. 870 95

Subunit c is normally present as an inner mitochondrial membrane component of the Fo sector of the ATP synthase complex, but in the late infantile form of neuronal ceroid lipofuscinosis (NCL) it was also found in lysosomes in high concentrations. Mechanism for specific accumulation of subunit c in lysosomes is not known. The rate of degradation of subunit c as measured by pulsechase and immunoprecipitation showed a marked delay of degradation in patients fibroblasts with late infantile form of NCL. There were no significant differences between control cells and cells with disease in the degradation of cytochrome oxidase subunit IV, an inner membrane protein of mitochondria. Measurement of labeled subunit c in mitochondrial and lysosomal fractions showed that the accumulation of labeled subunit c in the mitochondrial fraction can be detected before lysosomal appearance of radioactive subunit c, suggesting that subunit c accumulated as a consequence of abnormal catabolism in the mitochondrion and is transferred to lysosomes, through an autophagic process. There were no large differences of various lysosomal protease activities between control and patient cells. In patient cells sucrose loading caused a marked shift of lysosomal density, but did not a shift of subunit c containing storage body. The biosynthetic rate of subunit c and mRNA levels for P1 and P2 genes that code for it were almost the same in both control and patient cells. These findings suggest that a specific failure in the degradation of subunit c after its normal inclusion in mitochondria and its consequent accumulation in lysosomes.
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PMID:New insight into lysosomal protein storage disease: delayed catabolism of ATP synthase subunit c in Batten disease. 878 16

The effect of 6-ketocholestanol (kCh) on various natural and reconstituted membrane systems has been studied. 6-ketocholestanol (5 alpha-Cholestan-3 beta-ol-6-one), a compound increasing the membrane dipole potential, completely prevents or reverses the uncoupling action of low concentrations of the most potent artificial protonophore SF6847. This effect can be shown in the rat liver and heart muscle mitochondria, in the intact lymphocytes, in the Rhodobacter sphaeroides chromatophores, and in proteoliposomes with the heart muscle or Rh. sphaeroides cytochrome oxidase. The recoupling effect of kCh disappears within a few minutes after the kCh addition and cannot be observed at all at high SF6847 concentrations. Almost complete recoupling is also shown with FCCP, CCCP, CCP and platanetin. With 2,4-dinitrophenol, fatty acids and gramicidin, kCh is ineffective. With TTFB, PCP, dicoumarol, and zearalenone, low kCh concentrations are ineffective, whereas its high concentrations recouple but partially. The kCh recoupling is more pronounced in mitochondria, lymphocytes and proteoliposomes than in chromatophores. On the other hand, mitochondria, lymphocytes and proteoliposomes are much more sensitive to SF6847 than chromatophores. A measurable lowering of the electric resistance of a planar bilayer phospholipid membrane (BLM) are shown to occur at SF6847 concentrations which are even higher than in chromatophores. In BLMs, kCh not only fails to reverse the effect of SF6847, but even enhances the conductivity increase caused by this uncoupler. It is assumed that action of low concentrations of the SF6847-like uncouplers on coupling membranes involves cytochrome oxidase and perhaps some other membrane protein(s) as well. This involvement is inhibited by the asymmetric increase in the membrane dipole potential, caused by incorporation of kCh to the outer leaflet of the membrane.
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PMID:6-Ketocholestanol is a recoupler for mitochondria, chromatophores and cytochrome oxidase proteoliposomes. 903 Feb 61

Previous work from this laboratory revealed that alterations in the structure of the ccoNOQP operon of Rhodobacter sphaeroides 2.4.1 could lead to induction of the photosynthetic apparatus under aerobic growth conditions. Immediately downstream of the ccoNOQP operon is the rdxB gene, the first gene of the rdxBHIS cluster. The rdxB gene product is predicted to encode a membrane protein which can bind two [4Fe-4S] clusters. The ccoP gene product is a diheme cytochrome which is a component of the cbb3-type cytochrome oxidase. Under aerobic growth conditions, strains possessing ccoP and rdxB mutations both singly and in combination produced light-harvesting complexes, suggesting that normal functioning of these proteins is required to maintain repression of photosynthesis gene expression in the presence of oxygen. Analysis of the expression of puc::lacZ fusions under aerobic conditions revealed an approximately 12-fold increase in puc operon expression in the RDXB1 and CCOP1 mutant strains compared with that for wild-type 2.4.1. Similarly, puf::lacZ activity was observed to be elevated fourfold above wild-type levels. Further indication of the importance of the RdxB and CcoP proteins was derived from studies of mutant and wild-type cells grown under anoxygenic photosynthetic and nitrogen-fixing conditions. These mutant strains were observed to accumulate spheroidenone to approximately 50% or more of the total carotenoid. In wild-type cultures, spheroidenone normally accumulates to approximately 10 to 20% of the total carotenoid under the same growth conditions. This effect was most pronounced when both the rdxB and the ccoP mutations were present together in cells cultured under nitrogen-fixing photosynthetic growth conditions in which spheroidenone represented approximately 90% of the total carotenoid. We propose that mutations in the rdxB or ccoP gene may lead to changes in a membrane-generated redox signal or the accumulation of a critical redox intermediate in the mutant strains which results in increased photosynthesis gene expression under aerobic conditions by alteration of the activity of a transcriptional regulator(s) of photosynthesis gene expression. Mutations in these genes also appear to posttranscriptionally influence the terminal step of carotenoid biogenesis. Potential regulators interacting with an aberrant redox signal in the mutants and the possible nature of such a redox signal are discussed.
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PMID:Evidence for the role of redox carriers in photosynthesis gene expression and carotenoid biosynthesis in Rhodobacter sphaeroides 2.4.1. 906 41

The albino3 (alb3) mutant of Arabidopsis forms white or light yellow cotyledons and leaves and when germinated on soil does not survive beyond the seedling stage. The chloroplasts of the mutant are abnormal, as determined by electron microscopy, and contain reduced levels of chlorophyll. However, the chloroplasts of alb3 mutants are sufficiently differentiated to enable the expression of two nuclear genes whose transcription requires the presence of chloroplasts. The ALB3 gene was isolated by transposon tagging with the Activator/Dissociation transposable element system. ALB3 is a novel plant gene whose product shows homology to a bacterial membrane protein previously identified in five bacterial species and to a yeast protein, OXA1, and its human homolog. OXA1 is required in the mitochondria for proper assembly of the cytochrome oxidase complex. ALB3 does not have a function identical to OXA1 because mitochondrial cytochrome oxidase activity is not affected in the mutant, and immunogold labeling as well as chloroplast import experiments performed in vitro demonstrated that the ALB3 protein is present in chloroplast membranes. ALB3 might have a function related to that of OXA1 and be involved in the assembly of a chloroplast enzyme complex.
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PMID:ALBINO3, an Arabidopsis nuclear gene essential for chloroplast differentiation, encodes a chloroplast protein that shows homology to proteins present in bacterial membranes and yeast mitochondria. 916 49


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