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

The structural comparison of copper-containing proteins has provided a new dimension to the relationships suggested by sequence similarities. Ryden (1988) summarized the putative relationships, suggesting that a primordial single-domain cupredoxin evolved into the multidomain copper oxidases. The structures have revealed the fact that the differences reside primarily in insertions and deletions at junctions between secondary-structure elements. The mechanism of evolution (e.g., integration of new sequences into regions not essential to the Greek key fold) remains unknown. Which of the properties of a cupredoxin fold are necessary for function is the subject of site-directed mutagenesis studies. Can two of the ligands be interchanged (e.g., the upstream histidine and partially answered by the multidomain copper oxidase structure. The Tyr-Cys-Thr sequence in plastocyanin (in which threonine is a member of the hydrogen-bonding pair) is homologous with the His-Cys-His sequence in ascorbate oxidase. In the latter electron transfer is believed to flow from the type I copper (bound by the cysteine) to the trinuclear cluster, probably via these histidine residues. Hence, one might infer that the tyrosine and threonine have some role in electron transfer. Tyr-83 has been previously implicated in NMR studies as a primary site of electron transfer. The multi-copper protein structures have revealed interesting new features. The extra coppers are bound at domain interfaces, and can be single metals or the novel trinuclear cluster, depending on the availability of liganding histidines. A structural model of ceruloplasmin suggests that it will have at least two type I sites and, possibly, a third type I site such as stellacyanin (no methionine ligand), as well as a binding site for a trinuclear cluster. The similarity of the sequences of N2O reductases and a domain of cytochrome oxidase to the sequences of proteins with known structures suggests that these, too, will have Greek key domains. Galactose oxidase and hemocyanin do not have Greek key folds in their functional domains, although each does have a Greek key domain. The need for a Greek key fold remains obscure. The apoproteins are clearly stable without metals; there are examples other than immunoglobulins of Greek key folds. So far copper seems to be found in a very limited subset of structures; other chapters in this volume show that zinc, for example, has a much wider variety of environments in proteins, as does iron. It may be that the copper-containing Greek key proteins represent a very small evolutionary niche.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Copper protein structures. 179 5

relationship between levels of cAMP and catabolite repression in yeasts has been investigated. Strains of Saccharomyces cerevisiae, Schizosaccharomyces pombe and Kluyveromyces fragilis were used. The yeasts were grown on different carbon sources to attain various degrees of repression. Galactose repressed as much as glucose, while maltose was less effective. Full derepression was achieved with ethanol. The enzymes tested were fructose-bisphosphatase, malate dehydrogenase, glutamate dehydrogenase (NAD dependent), cytochrome oxidase and isocitrate lyase (this last enzyme was found to be absent in Schizosaccharomyces). The levels of cAMP were 2-3 times higher in the repressed conditions than in the derepressed ones. It is therefore concluded that in yeasts catabolite repression is not mediated by a lowering of the intracellular concentration of cAMP.
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PMID:Catabolite repression in yeasts is not associated with low levels of cAMP. 632 8

Galactose-specific lectins (Gal-lectins) were isolated from the mitochondrial fraction of prostate post-operational hyperplasic tissue of two diagnoses: benign prostate hyperplasic tissue with low-grade intraepithelial neoplasia (LGPIN) and benign prostate hyperplasic tissue with atypical adenomatous hyperplasia (AAH). They had similar molecular weight and other properties. Effects of these lectins were investigated in vitro model experiments on bovine liver cells mitochondrial properties. Time-dependent changes: (i) in the amount of H(2)O(2); (ii) redox state of Cu in cytochrome oxidase and (iii) redox state of heme in cytochrome a+a(3) (cyt a+a(3)) of cytochrome c oxidase complex were studied. Gal-lectins from both sources increase the amount of H(2)O(2) and decrease the redox state of Cu in cytochrome oxidase and heme in cyt a+a(3). However the Gal-lectin from tissue with more severed transformation (AAH) expresses significantly more strong and long-lasting influence. These effects are mediated by galactose binding domain of the lectins as are completely abolished by the inclusion of galactose in reaction medium. Accumulation of H(2)O(2) and long-lasting decrease in the redox state of key enzymes of mitochondrial respiration chain could induce defective functioning of these organelles and whole cells. Obtained data point the possible way, which enhances further transformation of prostate tissue by release of Gal-lectins from damaged mitochondria.
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PMID:Influence of beta-galactose-specific mitochondrial lectins from prostate hyperplasic tissue on mitochondrial properties. 1992 74