Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In phylogenetic trees based on comparison of nuclear small subunit rRNA sequences, Acanthamoeba castellanii (an amoeboid protozoon) is positioned near the base of the radiation leading to the animals, fungi and plants. However, the specific affiliation of this protist with the major multicellular lineages of eukaryotes is currently uncertain. To further explore the evolutionary position of A. castellanii, we have determined the complete primary sequence of its mitochondrial genome. We find that the circular mtDNA (41,591 bp; 70.6% A+T) encodes two rRNAs (small subunit and large subunit), 16 tRNAs and 33 proteins (17 subunits of the respiratory chain and 16 ribosomal proteins). As well, this genome contains eight open reading frames (ORFs) larger than 60 codons and of undefined function. Two of these ORFs (orf124 and orf142) have homologs in other mtDNAs ("orf25" and "orfB", respectively), three are unique to A. castellanii mtDNA (orf83, orf115 and orf349), and three are intronic ORFs. Among notable features of A. castellanii mtDNA are the following: (1) Genes and ORFs are all encoded on the same strand and are tightly packed, with only 6.8% of the total sequence not having an evident coding function and intergenic spacer sequences ranging from only 1 to 616 bp (average 64 bp). Ten pairs of protein-coding genes overlap by up to 38 bp and two subunits of cytochrome oxidase (COX1 and COX2) are specified by a single continuous ORF. (2) Only three introns, all group I and each containing a free-standing ORF, are present; these are localized in the 3'-half of the large subunit rRNA gene. (3) The genome encodes fewer than the minimal number of tRNA species required to support mitochondrial protein synthesis, suggesting that additional tRNAs are imported from the cytosol into A. castellanii mitochondria. Of the 16 tRNAs specified by A. castellanii mtDNA (one with an 8-nucleotide anticodon loop), 13 have been shown or are predicted to undergo a novel form of RNA editing within the acceptor stem. (4) A modified genetic code is used in which UGA specifies tryptophan. (5) Repeated sequences and obvious small sequence motifs that might represent regulatory elements are absent. In overall size, gene content and organizational pattern, A. castellanii mtDNA most closely resembles the mtDNA of the chlorophycean alga Prototheca wickerhamii (55,326 bp; 74.2% A+T), but is quite different in these respects from the mtDNA of Chlamydomonas reinhardtii (15,758 bp; 54.8% A+T), another chlorophycean alga, as well from characterized animal and fungal mitochondrial genomes.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The mitochondrial DNA of the amoeboid protozoon, Acanthamoeba castellanii: complete sequence, gene content and genome organization. 784 23

Saccharomyces cerevisiae cells carrying the mss2-1 pet mutation contain no Cox2 protein (cytochrome-c oxidase subunit 2), through COX2 transcripts are synthesized and processed normally. Gene MSS2 was cloned and sequenced. It is localized on chromosome IV. The Mss2 protein does not show any significant homology with published sequences.
...
PMID:The nuclear-encoded MSS2 gene is involved in the expression of the mitochondrial cytochrome-c oxidase subunit 2 (Cox2). 785 63

A new search for mitochondrial respiratory deficient mutants (Mit-) has been undertaken in order to accumulate a large number of point mutations in the coding portions of cytochrome-c-oxidase catalytic subunits and cytochrome b. Therefore, a mitochondrial DNA which retains the exons and lacks all the introns of the cytochrome oxidase subunit I and of the cytochrome-b split genes has been introduced into a strain carrying a nuclear recessive mutation affecting the adenine-nucleotide translocator, the op1 mutation, which is known to prevent the accumulation of large deletion petite mutants and this was used as the parental strain. After a moderate MnCl2 mutagenesis in order to limit multiple mutations, 105 Mit- mutants were isolated from 15,000 mutagenised clones in Saccharomyces cerevisiae. Mutations were mapped to the three catalytic subunits encoding genes (COX1, COX2 and COX3) of the cytochrome-c oxidase (70 mutations) and to the cytochrome-b gene (15 mutations). More than 50% of the mutants tested still exhibited mitochondrial translation products (subunits I, II and III), suggesting that they carry a missense mutation, rather than a nonsense mutation which would normally have led to a truncated protein. Mutations in the COX1 gene were allocated to four different subregions corresponding to exons 4 and 8 or to groups of exons, exons 1, 2, 3 or exons 5, 6, 7. Seven missense monosubstitution mutations and two frameshift mutations were also identified. The amino acid changes of the missense mutations were located in the vicinity of the CuB-heme alpha 3 binuclear centre ligands.
...
PMID:Genetic screening in Saccharomyces cerevisiae for large numbers of mitochondrial point mutations which affect structure and function of catalytic subunits of cytochrome-c oxidase. 838 19

Mitochondrial genomes from yeasts in the Dekkera/Brettanomyces/Eeniella group vary in size from 28 to 101 kb. Mapping of genes has shown that the three smallest genomes, of 28-42 kb, have the same gene order, whereas the three larger mitochondrial DNAs of 57-101 kb are rearranged relative to the smaller molecules and between themselves. To examine the relationships between these genomes, a phylogenetic tree has been constructed by sequence comparison of the mitochondrial-encoded cytochrome oxidase subunit gene (COX2) from the six species. Contrary to expectation, the tree shows that the larger rearranged genomes are more closely related than the smaller mtDNAs. This result indicates that the gene order of the smaller mtDNAs (28-42 kb) is ancestral and that larger mtDNA molecules (57-101 kb) are more prone to rearrangement than smaller forms.
...
PMID:Larger rearranged mitochondrial genomes in Dekkera/Brettanomyces yeasts are more closely related than smaller genomes with a conserved gene order. 838 13

To examine normal and aberrant translation initiation in Saccharomyces cerevisiae mitochondria, we fused the synthetic mitochondrial reporter gene ARG8m to codon 91 of the COX2 coding sequence and inserted the chimeric gene into mitochondrial DNA (mtDNA). Translation of the cox2(1-91)::ARG8m mRNA yielded a fusion protein precursor that was processed to yield wild-type Arg8p. Thus mitochondrial translation could be monitored by the ability of mutant chimeric genes to complement a nuclear arg8 mutation. As expected, translation of the cox2(1-91)::ARG8m mRNA was dependent on the COX2 mRNA-specific activator PET111. We tested the ability of six triplets to function as initiation codons in both the cox2(1-91)::ARG8m reporter mRNA and the otherwise wild-type COX2 mRNA. Substitution of AUC, CCC or AAA for the initiation codon abolished detectable translation of both mRNAs, even when PET111 activity was increased. The failure of these mutant cox2(1-91)::ARG8m genes to yield Arg8p demonstrates that initiation at downstream AUG codons, such as COX2 codon 14, does not occur even when normal initiation is blocked. Three mutant triplets at the site of the initiation codon supported detectable translation, with efficiencies decreasing in the order GUG, AUU, AUA. Increased PET111 activity enhanced initiation at AUU and AUA codons. Comparisons of expression, at the level of accumulated product, of cox2(1-91)::ARG8m and COX2 carrying these mutant initiation codons revealed that very low-efficiency translation can provide enough Cox2p to sustain significant respiratory growth, presumably because Cox2p is efficiently assembled into stable cytochrome oxidase complexes.
...
PMID:In vivo analysis of mutated initiation codons in the mitochondrial COX2 gene of Saccharomyces cerevisiae fused to the reporter gene ARG8m reveals lack of downstream reinitiation. 1066 64

Nuclear mutants of Saccharomyces cerevisiae assigned to complementation group G34 are respiratory-deficient and lack cytochrome oxidase activity and the characteristic spectral peaks of cytochromes a and a(3). The corresponding gene was cloned by complementation, sequenced, and identified as reading frame YGR062C on chromosome VII. This gene was named COX18. The COX18 gene product is a polypeptide of 316 amino acids with a putative amino-terminal mitochondrial targeting sequence and predicted transmembrane domains. Respiratory chain carriers other than cytochromes a and a(3) and the ATPase complex are present at near wild-type levels in cox18 mutants, indicating that the mutations specifically affect cytochrome oxidase. The synthesis of Cox1p and Cox3p in mutant mitochondria is normal whereas Cox2p is barely detected among labeled mitochondrial polypeptides. Transcription of COX2 does not require COX18 function, and a chimeric COX3-COX2 mRNA did not suppress the respiratory defect in the null mutant, indicating that the mutation does not impair transcription or translation of the mRNA. Western analysis of cytochrome oxidase subunits shows that inactivation of the COX18 gene greatly reduces the steady state amounts of subunit 2 and results in variable decreases in other subunits of cytochrome oxidase. A gene fusion expressing a biotinylated form of Cox18p complements cox18 mutants. Biotinylated Cox18p is a mitochondrial integral membrane protein. These results indicate Cox18p to be a new member of a group of mitochondrial proteins that function at a late stage of the cytochrome oxidase assembly pathway.
...
PMID:Cloning and characterization of COX18, a Saccharomyces cerevisiae PET gene required for the assembly of cytochrome oxidase. 1080 34

As part of our goal to reconstruct human evolution at the DNA level, we have been examining changes in the biochemical machinery for aerobic energy metabolism. We find that protein subunits of two of the electron transfer complexes, complex III and complex IV, and cytochrome c, the protein carrier that connects them, have all undergone a period of rapid protein evolution in the anthropoid lineage that ultimately led to humans. Indeed, subunit IV of cytochrome c oxidase (COX; complex IV) provides one of the best examples of positively selected changes of any protein studied. The rate of subunit IV evolution accelerated in our catarrhine ancestors in the period between 40 to 18 million years ago and then decelerated in the descendant hominid lineages, a pattern of rate changes indicative of positive selection of adaptive changes followed by purifying selection acting against further changes. Besides clear evidence that adaptive evolution occurred for cytochrome c and subunits of complexes III (e.g., cytochrome c(1)) and IV (e.g., COX2 and COX4), modest rate accelerations in the lineage that led to humans are seen for other subunits of both complexes. In addition the contractile muscle-specific isoform of COX subunit VIII became a pseudogene in an anthropoid ancestor of humans but appears to be a functional gene in the nonanthropoid primates. These changes in the aerobic energy complexes coincide with the expansion of the energy-dependent neocortex during the emergence of the higher primates. Discovering the biochemical adaptations suggested by molecular evolutionary analysis will be an exciting challenge.
...
PMID:Molecular evolution of aerobic energy metabolism in primates. 1116 39

A phylogenetic analysis was conducted upon ten strains of the psychrophobic yeast species Arxiozyma telluris using nuclear rDNA (18S and 26S) and mitochondrial cytochrome-c oxidase subunit II (COX2) gene sequences. Strains examined included those described originally as Candida slooffii, Torulopsis bovina (= Candida bovina) and Torulopsis pintolopesii (= Candida pintolopesii), which are all currently accepted as synonyms of Arxiozyma telluris. Comparative 18S rDNA sequence analysis showed that these strains formed a genealogically highly related group, which was phylogenetically distinct from any other ascomycetous species studied. The results showed that A. telluris, as currently described, appears to be composed of a complex of closely related but nevertheless separate taxa. rDNA and COX2 gene sequence data revealed that CBS 1787T, the type strain of C. pintolopesii, the currently recognized asexual form (anamorph) of A. telluris, along with strains CBS 2676 and CBS 2985 formed a distinct taxon that is phylogenetically separate from A. telluris. Similarly, the sequence data also showed that C. slooffii is a distinct taxon and support the reinstatement of this species. However, with regard to the relationship between the type strains of A. telluris (CBS 2685T) and C bovina (CBS 2760T), discrepancies were observed between the rDNA and COX2 sequence datasets, and these results are discussed in more detail.
...
PMID:Phylogenetic analysis of the psychrophobic yeast Arxiozyma telluris and the reinstatement of Candida pintolopesii (van Uden) Meyer et Yarrow and Candida slooffii van Uden et do Carmo Sousa. 1159 26

Cytochrome oxidase subunit 2 (Cox2p) is synthesized on the matrix side of the mitochondrial inner membrane, and its N- and C-terminal domains are exported across the inner membrane by distinct mechanisms. The Saccharomyces cerevisiae nuclear gene MSS2 was previously shown to be necessary for Cox2p accumulation. We have used pulse-labeling studies and the expression of the ARG8(m) reporter at the COX2 locus in an mss2 mutant to demonstrate that Mss2p is not required for Cox2p synthesis but rather for its accumulation. Mutational inactivation of the proteolytic function of the matrix-localized Yta10p (Afg3p) AAA-protease partially stabilizes Cox2p in an mss2 mutant but does not restore assembly of cytochrome oxidase. In the absence of Mss2p, the Cox2p N terminus is exported, but Cox2p C-terminal export and assembly of Cox2p into cytochrome oxidase is blocked. Epitope-tagged Mss2p is tightly, but peripherally, associated with the inner membrane and protected by it from externally added proteases. Taken together, these data indicate that Mss2p plays a role in recognizing the Cox2p C tail in the matrix and promoting its export.
...
PMID:Peripheral mitochondrial inner membrane protein, Mss2p, required for export of the mitochondrially coded Cox2p C tail in Saccharomyces cerevisiae. 1160 2

The post-transcriptional role of Mss51p in mitochondrial gene expression is of great interest since MSS51 mutations suppress the respiratory defect caused by shy1 mutations. SHY1 is a Saccharomyces cerevisiae homolog of human SURF1, which when mutated causes a cytochrome oxidase assembly defect. We found that MSS51 is required for expression of the mitochondrial reporter gene ARG8(m) when it is inserted at the COX1 locus, but not when it is at COX2 or COX3. Unlike the COX1 mRNA-specific translational activator PET309, MSS51 has at least two targets in COX1 mRNA. MSS51 acts in the untranslated regions of the COX1 mRNA, since it was required to synthesize Arg8p when ARG8(m) completely replaced the COX1 codons. MSS51 also acts on a target specified by the COX1 coding region, since it was required to translate either COX1 or COX1:: ARG8(m) coding sequences from an ectopic COX2 locus. Mss51p was found to interact physically with newly synthesized Cox1p, suggesting that it could coordinate Cox1p synthesis with insertion into the inner membrane or cytochrome oxidase assembly.
...
PMID:Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly synthesized Cox1p. 1459 91


1 2 3 Next >>

---