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Query: UNIPROT:P06889 (Mol)
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In Saccharomyces cerevisiae, subunit V of the inner mitochondrial membrane protein complex cytochrome c oxidase is encoded by two nonidentical genes, COX5a and COX5b. Both genes are present as single copies in S. cerevisiae and in several other Saccharomyces species. Nucleotide sequencing studies with the S. cerevisiae COX5 genes reveal that they encode proteins of 153 and 151 amino acids, respectively. Overall, the coding sequences of COX5a and COX5b have nucleotide and protein homologies of 67 and 66%, respectively. They are saturated for nucleotide substitutions that result in a synonomous codon, indicating a long divergence time between these two genes. Nucleotide sequences flanking the COX5a and COX5b coding regions exhibit no significant homology. The COX5a protein, pre-subunit Va, contains a 20-amino-acid leader peptide, whereas the COX5b protein, pre-subunit Vb, contains a 17-amino-acid leader peptide. These two leader peptides exhibit only 45% homology in the primary sequence, but have similar predicted secondary structures. By analyzing the RNA transcripts from both genes we have found that COX5a is a contiguous gene but that COX5b contains an intron. Surprisingly, the COX5b intron interrupts the AUG codon that initiates translation of the pre-subunit Vb polypeptide and contains a 5' donor splice sequence that differs from that normally found in yeast introns.
Mol Cell Biol 1987 Oct
PMID:Structural analysis of two genes encoding divergent forms of yeast cytochrome c oxidase subunit V. 282 89

In Saccharomyces cerevisiae, COX5a and COX5b encode two distinct forms of cytochrome c oxidase subunit V, Va and Vb, respectively. To determine the relative contribution of COX5a and COX5b to cytochrome c oxidase function, we have disrupted each gene. Cytochrome c oxidase activity levels and respiration rates of strains carrying null alleles of COX5a or COX5b or both indicate that some form of subunit V is required for cytochrome c oxidase function and that COX5a is much more effective than COX5b in providing this function. Wild-type respiration is supported by a single copy of either COX5a or COX5ab (a constructed chimeric gene sharing 5' sequences with COX5a). In contrast, multiple copies of COX5b or COX5ba (a chimeric gene with 5' sequences from COX5b) are required to support wild-type respiration. These results suggest that the decreased effectiveness of COX5b is due to inefficiency in gene expression rather than to any deficiency in the gene product, Vb. This conclusion is supported by two observations: (i) a COX5a-lacZ fusion gene produces more beta-galactosidase than a COX5b-lacZ fusion gene, and (ii) the COX5a transcript is significantly more abundant than the COX5b transcript or the COXsba transcript. We conclude that COX5a is expressed more efficiently than COX5b and that, although mature subunits Va and Vb are only 67% homologous, they do not differ significantly in their ability to assemble and function as subunits of the holoenzyme.
Mol Cell Biol 1987 Oct
PMID:Differential effectiveness of yeast cytochrome c oxidase subunit genes results from differences in expression not function. 282 90

The integral mitochondrial membrane protein cytochrome c oxidase (ferrocytochrome-c:oxygen oxidoreductase, EC 1.9.3.1) was crystallized from solutions of the protein from bovine heart isolated as described earlier [Yoshikawa, S. & Caughey, W. S. (1982) J. Biol. Chem. 257, 412-420]. Crystallinity was demonstrated by x-ray diffraction. Microcrystals (tetragonal prisms, 0.02 mm in the largest dimension) were obtained in high yield with retention of activity and contained Fe, Cu, Zn, and Mg in approximate atom ratios of 1.0:1.25:0.5:0.5, respectively. Analysis of the amino acid residues and the tightly bound detergent support an apparent molecular mass of about 200 kDa, of which 150 kDa is protein (1316 +/- 66 amino acids) and 50 kDa is detergent (Brij 35). Seven major polypeptides are evident by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Adjustments in buffer concentration and other conditions have yielded much larger green crystals, hexagonal bipyramids; a crystal 0.3 X 0.5 X 0.7 mm gave x-ray diffractions as high as 8-A resolution and a space group of P6(2) or P6(4), and cell dimensions of a = b = 174.5 A, c = 282.2 A, alpha = beta = 90 degrees, and gamma = 120 degrees were obtained. A reasonable value of 3.1 A3/Da for Vm, the average space per dalton of protein in the crystal, was obtained for the asymmetric unit, which contains four irons and is a dimer of two minimal catalytic units. Cylindrical dimers (80 X 100 A) estimated from two-dimensional electron diffraction studies [Fuller, S. D., Capaldi, R. A. & Henderson, R. (1979) J. Mol. Biol. 134, 305-327] pack well in the crystal lattice with the symmetry of the space group of the crystal. The crystallization procedure developed is useful in purification of the enzyme and shows promise for the production of crystals of sufficiently high order to gain improved structural information from x-ray diffraction.
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PMID:Crystalline cytochrome c oxidase of bovine heart mitochondrial membrane: composition and x-ray diffraction studies. 283 Jun 15

We have identified and isolated a novel yeast nuclear gene (SCO1) which is essential for accumulation of the mitochondrially synthesized subunit II of cytochrome c oxidase (CoxII). Analysis of the mitochondrial translation products in a sco1-1 mutant reveals a strong reduction in CoxII. Examination of mitochondrial transcripts by Northern blot hybridization shows that transcription and transcript maturation of OXI1, the gene coding for CoxII, is not affected. Therefore the SCO1 gene product must be involved in a post-transcriptional step in the synthesis of CoxII. We have isolated a 1.7 kb DNA fragment from a yeast gene bank which carries the functional SCO1 gene. Two RNA species of 0.9 kb and 1.2 kb, respectively, hybridize with this DNA fragment, which is localized on chromosome II. Cells whose chromosomal 1.7 kb fragment has been replaced by the yeast URA3 gene fail to accumulate CoxII and in addition subunit I of cytochrome c oxidase (CoxI). The possibility that the SCO1 gene product is bifunctional, i.e. required for both CoxI and CoxII accumulation, is discussed.
Mol Gen Genet 1988 Mar
PMID:SCO1, a yeast nuclear gene essential for accumulation of mitochondrial cytochrome c oxidase subunit II. 283 35

In a previous report, mitochondria were proposed as a subcellular structure where recognition sites for peripheral benzodiazepine ligands are located in adrenal glands. The present study examines the subcellular distribution of specific binding sites for PK 11195 in eight tissues and compares the relative densities of these binding sites in mitochondrial-enriched fractions with the relative activities of two mitochondrial marker enzymes. In all eight tissues examined, PK 11195 binding sites were found to subfractionate in a manner nearly identical to that of the mitochondrial enzyme succinate dehydrogenase. The subcellular distribution patterns of specific PK 11195 binding sites were unrelated to the distribution patterns of marker enzymes for plasma membranes, lysosomes, or endoplasmic reticulum. Scatchard analyses of mitochondrial fractions from all eight tissues demonstrated a greater than 100-fold difference in the densities of PK 11195 binding sites, the extremes being 140 and 1 pmol/mg of protein in adrenal and brain tissues, respectively. There was no correlation between the relative density of PK 11195 binding sites and the specific activities of succinate dehydrogenase and cytochrome c oxidase. These results suggest that the density of peripheral-type benzodiazepine receptors in mitochondria is tissue dependent and apparently regulated independently of the mechanisms by which these two mitochondrial enzymes are expressed or function. The photoaffinity probe PK 14105 was used to photolabel the peripheral-type benzodiazepine binding sites of mitochondrial fractions prepared from the eight tissues. In all preparations, a 17,000-Da polypeptide is specifically labeled as determined by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Thus, it appears that the protein recognition site for isoquinoline carboxamides of peripheral-type benzodiazepine receptor complexes is similar in all mitochondrial preparations.
Mol Pharmacol 1988 Sep
PMID:Molecular characterization and mitochondrial density of a recognition site for peripheral-type benzodiazepine ligands. 284 47

The distribution of [3H]leukotriene D4 [( 3H]LTD4) receptors in subcellular membrane fractions obtained from sheep tracheal smooth muscle was studied. Using differential centrifugation and discontinuous sucrose density gradient centrifugation, the subcellular membranes were separated into six fractions. The [3H]LTD4 receptor distribution profile in these fractions correlated with markers for the plasma membrane (5'-nucleotidase and alkaline phosphodiesterase) and did not correlate with markers for the mitochondria (cytochrome c oxidase and succinate-dependent cytochrome c reductase). The dissociation constant (Kd) and maximum number of binding sites (Bmax) for [3H]LTD4 binding to the receptors in the crude mixture of membranes (PII) were 0.38 +/- 0.2 nM and 77 +/- 14 fmol/mg of protein, respectively. The Kd and Bmax of [3H]LTD4 binding to the receptors in the plasma membrane-enriched fraction (FII) were 0.40 +/- 0.2 nM and 268 +/- 46 fmol/mg of protein, respectively. The specificity profile of the [3H]LTD4 receptors in the plasma membrane-enriched fraction was equivalent to that observed in the crude membrane and correlated with the agonist myotonic activities in the smooth muscle contraction assay system. Furthermore, the binding of [3H]LTD4 to the plasma membrane receptors was modulated by guanine nucleotides in a manner analogous to that observed in crude membranes, suggesting that agonist interaction with the receptors was regulated by guanine nucleotide binding protein. These results suggest that, in sheep tracheal smooth muscle, the plasma membrane is the primary location of specific LTD4 receptors.
Mol Pharmacol 1988 Oct
PMID:Subcellular localization of leukotriene D4 receptors in sheep tracheal smooth muscle. 284 53

In Saccharomyces cerevisiae, the COX5a and COX5b genes encode two forms of cytochrome c oxidase subunit V, Va and Vb. We report here that heme increases COX5a expression and decreases COX5b expression and that the HAP2 and REO1 genes are involved in positive regulation of COX5a and negative regulation of COX5b, respectively. Heme regulation of COX5a and COX5b may dictate which subunit V isoform is available for assembly into cytochrome c oxidase under conditions of high- and low-oxygen tension.
Mol Cell Biol 1988 Oct
PMID:Differential regulation of the two genes encoding Saccharomyces cerevisiae cytochrome c oxidase subunit V by heme and the HAP2 and REO1 genes. 284 35

Using a polyclonal antibody raised against bovine heart cytochrome c oxidase, the occurrence of this mitochondrial marker enzyme has been investigated in 63 kidney tumors (ten renal oncocytomas, 43 renal cell carcinomas and ten tubulopapillary adenomas) as well as in normal renal tissue by an immunoperoxidase method (PAP-technique). The differentiation between renal oncocytomas and mitochondria-rich carcinomas represents a problem of histopathology since these tumors have a different prognosis and require different patient managements. The strong immunoreactivity in renal oncocytomas contrasted with the much weaker reactivity in renal carcinomas and adenomas. Even mitochondria-rich (granular cell type) carcinomas exhibited only moderate staining intensity. Furthermore, single strongly stained oncocytes or small complexes were sometimes detected in normal renal tissue. The demonstration of marked differences in enzyme content between renal oncocytomas and granular cell carcinomas renders this method suitable for unequivocal distinction between these renal neoplasms. The antibody proved to be a valuable marker for detecting "true" oncocytic transformation in renal tumors and was useful in defining even single oncocytes or small oncocytic lesions.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Renal oncocytoma. I. Cytochrome c oxidase in normal and neoplastic renal tissue as detected by immunohistochemistry--a valuable aid to distinguish oncocytomas from renal cell carcinomas. 290 89

Chicken embryo fibroblasts in uridine-containing medium are inherently resistant to the growth-inhibitory effect of ethidium bromide. The drug was found to inhibit the incorporation of [3H]thymidine into mitochondrial DNA circular molecules. Mitochondrial DNA was quantitated by DNA-DNA reassociation kinetics with a probe of chicken liver mitochondrial DNA. A mean number of 604 copies of mitochondrial DNA per cell was found. This number decreased progressively in cells exposed to ethidium bromide, and by day 13 ca. one copy of mitochondrial DNA was detected per cell. When the cells were then transferred to drug-free medium, the number of copies increased very slowly as a function of time. On the other hand, analyses of DNA extracted from cell populations exposed to ethidium bromide for 20 or more days, with or without subsequent transfer to drug-free medium, revealed very little or no mitochondrial DNA by reassociation kinetics or by Southern blot hybridization of AvaI- or HindIII-digested total cellular DNA. As a result of the elimination of mitochondrial DNA molecules, the establishment of cell populations with a respiration-deficient phenotype was confirmed by measuring cytochrome c oxidase activity as a function of the number of cell generations and the absorption spectrum of mitochondrial cytochromes.
Mol Cell Biol 1985 May
PMID:Ethidium bromide-induced loss of mitochondrial DNA from primary chicken embryo fibroblasts. 298 77

We have determined the nucleotide sequence of a 3.3 kilobase segment of the kDNA maxicircle of Trypanosoma brucei brucei 164. The nucleotide sequence and its predicted translated sequence have homology to cytochrome c oxidase subunits I and II (CO I and II) and mammalian unidentified reading frame 1 (URF 1). Amino acid homology to CO II extends for 170 residues from the amino terminus in one reading frame and then continues in another reading frame for 39 residues to the carboxyl terminus. Similar results have been obtained for Leishmania tarentolae [de la Cruz, V.F., Neckelmann, N. and Simpson, L. (1984) J. Biol. Chem., in press] and T. brucei 427 [Hensgens, L.A.M., Brackenhoff, J., De Vries, B.F., Sloof, P., Tromp, M.C., Van Boom, J.H. and Benne, R. (1984) Nucleic Acids Res. 12, 7327-7344]. This may indicate that novel events are required for expression of this gene. Amino acid homology to URF 1 exists predominantly at the amino terminal end although no corresponding AUG codon occurs in this area. An alternative initiation codon may therefore be utilized by trypanosome mitochondria. Two other open reading frames (ORFs) were detected and these are discussed with reference to transcripts from this region. ORFs corresponding to transcripts are organized compactly and are distributed more equally on both strands compared to ORFs of other mitochondrial systems.
Mol Biochem Parasitol 1985 May
PMID:Identification of mitochondrial genes in Trypanosoma brucei and homology to cytochrome c oxidase II in two different reading frames. 298 84


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