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)

Neurochemical and psychopharmacological studies of rats were designed to examine four hypotheses which have been proposed to account for the development of behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate (DFP). The fact that the activity of the enzymes, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase, did not change concomitantly with behavioral measures during chronic treatment with DFP suggests that nonspecific metabolic changes are unlikely mechanisms of behavioral tolerance. Similarly, a lack of change in choline acetylase activity coupled with constantly high acetylcholine levels (140%) and low cholinesterase activity (28.5%) tends to eliminate end-product inhibition of acetylcholine synthesis as a primary mechanism of tolerance to DFP. Alpha-Methyl-p-tyrosine in doses to 150 mg/kg affected the behaviors of control and DFP-treated rats to a comparable degree, offering no support for the hypothesis that a redundant adrenergic system may replace the cholinergic system during the development of tolerance to DFP. In contrast to these various negative findings, pilocarpine was less effective in suppressing the responding of rats tolerant to DFP than that of control subjects. This confirms other evidence indicating that a decreased sensitivity of cholinergic (muscarinic) receptors is one mechanism underlying the development of tolerance to DFP.
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PMID:Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate. 16 30

The complete amino acid sequence of the heme alpha-containing subunit V of bovine heart cytochrome oxidase was determined to be: H2N-Ser-His-Gly-Ser-His-Glu-Thr-Asp-Glu-Glu-Phe-Asp-Ala-Arg-Trp-Val-Thr-Tyr-Phe-Asn-Lys-Pro-Asp-Ile-Asp-Ala-Trp-Glu-Leu-Arg-Lys-Gly-Met-Asn-Thr-Leu-Val-Gly-Tyr-Asp-Leu-Val-Pro-Glu-Pro-Lys-Ile-Ile-Asp-Ala-Ala-Leu-Arg-Ala-Cys-Arg-Arg-Leu-Asn-Asp-Phe-Ala-Ser-Ala-Val-Arg-Ile-Leu-Glu-Val-Val-Lys-Asp-Lys-Ala-Gly-Pro-His-Lys-Glu-Ile-Tyr-Pro-Tyr-Val-Ile-Gln-Glu-Leu-Arg-Pro-Thr-Leu-Asn-Glu-Leu-Gly-Ile-Ser-Thr-Pro-Glu-Glu-Leu-Gly-Leu-Asp-Lys-Val-COOH. The subunit V is a single polypeptide which consists of 109 amino acid residues. The protein contains 48.6% hydrophobic residues and 34.0% hydrophilic residues and it is an acidic protein having a net charge of -3 at neutral pH. The molecular weight of subunit V was calculated to be 12,436 and that for the heme alpha-containing polypeptide was 13,295.
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PMID:Amino acid sequence of subunit V of bovine heart cytochrome oxidase, the heme alpha-containing subunit. 22 Feb 24

Between pH approximately 4 and 10 cobaltocytochrome c (Cocyt-c) gives an electron paramagnetic resonance (EPR) spectrum with g parallel = 2.035, g the perpendicular = 2.223, CoA PARALLEL = 61.4 G, CoA the perpendicular = 49.8 G, NA parallel = 15.3 G, and NA THE PERPENDICULAR = 12.5 G. Comparisons with the EPR spectra of deoxycobaltomyoglobin, deoxycobaltohemoglobin, and model compounds and together with other evidence showed cobaltocytochrome c to have Met-80 and His-18 as its axial ligands. The protons of these ligands are seen as resonances shifted by the ring-current field of the porphyrin in the 300-MHZ 1H nuclear magnetic resonance (NMR) spectra of cobalticytochrome c (Cocyt-c+). The methyl and gamma-methylene protons of Met-80 in this molecule occupy positions with respect to heme c which are somewhat different from those in ferrocytochrome c. The 1H NMR spectra also showed that the methyl groups of Leu-32, Ile-75, Thr-63, thioether bridges, and the porphyrin ring in the cobalt protein are in the same state as in native enzyme; the same is also true for Tyr-59, His-26, and His-33 and also possibly Tyr-67, Tyr-74, and Phe-82. Above pH 11, Cocyt-c is converted to a five-coordinated form having g parallel = 2.026, g the perpendicular = 2.325, CoA parallel = 80 G, CoA the perpendicular approximately 10 G, NA parallel = 17.5 G, and NA the perpendicular not resolved. Below pH 1.0 the EPR spectrum of Cocyt-c is also five-coordinated with g parallel = 2.014, g the perpendicular = 2.359, CoA parallel = 93.8 G, and CoA the perpendicular = 38.8 G. The axial ligands in the alkaline and the acidic forms of Cocyt-c are His-18 and Met-80, respectively. New prominent proton resonance peaks are observed in cobalt-cytochrome c which are either absent or weak in native cytochrome c. These are situated at 3.0, 1.7, and 1.44 ppm, attributable, respectively, to the epsilon-CH2, DELTA-CH2 + beta-CH2, and gamma-CH2 of lysyl residues in random-coil-peptides. From the areas of these peaks, it is estimated that one-two lysyl residues in Cocyt-c have been modified; four-five lysyl residues in Cocyt-c+ have been modified. These alterations of surface charged groups are probably responsible for the lowered reactivity of Cocyt-c with cytochrome oxidase and the lack of reactivity of Cocyt-c+ with several cytochrome reductase systems.
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PMID:Cobalt-cytochrome c. II. Magnetic resonance spectra and conformational transitions. 24 Mar 81

We have analyzed a mutation in the mitochondrial gene oxi3 coding for subunit I of cytochrome-oxidase in the yeast Saccharomyces cerevisiae. This mutation replaces one of the seven invariant histidines of the polypeptide (position 378) by a tyrosine, and leads to a respiratory deficient phenotype. A total of 157 revertants, which have recovered the ability to grow on a respiratory substrate, have been selected from this mutant (tyrosine 378). The nature of the reversion has been analysed by a rapid screening procedure and 32 of the revertants have been sequenced. They are all true back-mutations reintroducing the histidine in position 378. This very exceptional situation suggests that this histidine is a ligand of the redox center of cytochrome oxidase.
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PMID:The unusual reversion properties of a mitochondrial mutation in the structural gene of subunit I of cytochrome oxidase of Saccharomyces cerevisiae reveal a probable histidine ligand of the redox center. 131 5

Transcription factor nuclear respiratory factor 1 (NRF-1) was originally identified as an activator of the cytochrome c gene and subsequently found to stimulate transcription through specific sites in other nuclear genes whose products function in the mitochondria. These include subunits of the cytochrome oxidase and reductase complexes and a component of the mitochondrial DNA replication machinery. Here we establish that a functional recognition site for NRF-1 is present in the ATP synthase gamma-subunit gene extending the proposed respiratory role of NRF-1 to complex V. In addition, biologically active NRF-1 sites are found in genes encoding the eukaryotic translation initiation factor 2 alpha-subunit and tyrosine aminotransferase, both of which participate in the rate-limiting step of their respective pathways of protein biosynthesis and tyrosine catabolism. The recognition sites from each of these genes form identical complexes with NRF-1 as established by competition binding assays, methylation interference footprinting, and UV-induced DNA cross-linking. Cloned oligomers of each NRF-1 binding site also stimulate the activity of a truncated cytochrome c promoter in transfected cells. The NRF-1 binding activities for the various target sites copurified approximately 33,000-fold and resided in a single protein of 68 kDa. These observations further support a role for NRF-1 in the expression of nuclear respiratory genes and suggest it may help coordinate respiratory metabolism with other biosynthetic and degradative pathways.
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PMID:Nuclear respiratory factor 1 activation sites in genes encoding the gamma-subunit of ATP synthase, eukaryotic initiation factor 2 alpha, and tyrosine aminotransferase. Specific interaction of purified NRF-1 with multiple target genes. 134 57

The gene (coxII) encoding subunit II of Rhodobacter sphaeroides cytochrome c oxidase (cytochrome aa3) has been isolated by screening a genomic DNA library in phage lambda with a probe derived from coxII of Paracoccus denitrificans. A 2-kb fragment containing coxII DNA was subcloned into the phage M13mp18 and the sequence determined. The 2-kb insert contains the entire coding region for coxII gene, including the ATG start codon and a TGA stop codon. The deduced amino acid (aa) sequence of subunit II of R. sphaeroides shows regions of substantial homology to the corresponding subunit of the bovine mitochondrial oxidase (63% overall) and P. denitrificans oxidase (68% overall). The postulated redox-active copper ion (CuA) binding site involving two Cys and two His residues (as well as an alternative Met residue) is conserved among these species, along with four invariant acidic aa residues (two Asp and two Glu) that may be involved in interactions with cytochrome c, and a region of aromatic residues (Tyr-Gln-Trp-Tyr-Trp-Gly-Tyr-Glu-Tyr) which is postulated to play a role in electron transfer. Hydropathy profile analysis suggests that while the bovine COXII secondary structure contains two transmembrane helices, the R. sphaeroides subunit II has a third such helix that may function as part of a signal sequence, as suggested for P. denitrificans.
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PMID:The gene encoding cytochrome c oxidase subunit II from Rhodobacter sphaeroides; comparison of the deduced amino acid sequence with sequences of corresponding peptides from other species. 164 8

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

Mutation of conserved Phe-82 of yeast iso-1 cytochrome c to Tyr, Gly, Ser, Leu, or Ile affects binding to and reaction with cytochrome-c oxidase from beef heart. The observed changes of binding and kinetic constants reflect mutation-induced rearrangements in the heme vicinity brought about by the replacement of Phe-82. Such conformational rearrangements are also revealed by altered circular dichroism spectra of the oxidase-bound mutant cytochromes c. Variations in Km for cytochrome c oxidation do not parallel variations in Kd, the dissociation constant for binding of cytochrome c to the oxidase. This observation does not support an enzymatic mechanism in which the rate of cytochrome c oxidation is governed by product dissociation.
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PMID:Binding and oxidation of mutant cytochromes c by cytochrome-c oxidase. 253 28

The role of insulin in norepinephrine turnover (NE) and thermogenesis in brown adipose tissue (BAT) after acute cold-exposure was studied using streptozocin (STZ)-induced diabetic rats. NE turnover was estimated by the NE synthesis inhibition technique with alpha-methyl-p-tyrosine. BAT thermogenesis was estimated by measuring mitochondrial guanosine-5'-diphosphate (GDP), cytochrome oxidase activity and mitochondrial oxygen consumption in BAT at an ambient temperature of 22 degrees C and during a six-hour cold-exposure at 4 degrees C. In insulin-deficient diabetic rats, the NE turnover, mitochondrial GDP binding, cytochrome oxidase activity and mitochondrial oxygen consumption in BAT at 22 degrees C were significantly reduced, compared with those of control rats. Treatment of STZ-induced diabetic rats with insulin prevented a decrease in NE turnover and BAT thermogenesis. Acute cold-exposure increased the NE turnover of BAT in insulin-deficient diabetic rats. The BAT thermogenic response to acute cold-exposure, however, did not occur in insulin-deficient diabetic rats. These results suggest that insulin is not essential in potentiating NE turnover in BAT after acute cold-exposure, but is required for cold-induced thermogenesis.
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PMID:The role of insulin in norepinephrine turnover and thermogenesis in brown adipose tissue after acute cold-exposure. 255 47

Lysine 32 has been previously implicated by chemical modification and modeling studies as a key component of the domain which controls recognition and binding of cytochrome c to its physiological partners, e.g. cytochrome b2, cytochrome c peroxidase, and cytochrome oxidase. In order to quantitate the importance of this residue, we have investigated the role of Lys-32 in the reactivity of cytochrome c in redox reactions in vitro and in vivo with protein partners by using a series of altered forms of iso-1-cytochrome c from the yeast Saccharomyces cerevisiae in which Lys-32 is replaced by Leu-32, Gln-32, Trp-32, and Tyr-32. Leu-32 and Gln-32 represent substitutions which change charge without seriously affecting the steric bulk of the side chain or the stability of the protein. For the Leu-32- and Gln-32-altered proteins, steady state kinetic studies with cytochrome c peroxidase, cytochrome b2, and cytochrome oxidase showed that neither of the steady state kinetic parameters, Km nor Vmax, were substantially modified by mutation. Studies of single turnover kinetics with a small molecule (ascorbate) or within bound complexes with either cytochrome b5 or cytochrome c peroxidase demonstrated that redox kinetics are only slightly affected by these substitutions. NMR experiments demonstrated that the Gln-32-altered protein can still bind strongly to a physiological partner, cytochrome c peroxidase. Growth in lactate medium demonstrated that the activity in vivo compared with the normal value was reduced to only 85% with the Gln-32- and Leu-32-altered proteins and to 65% with the Trp-32- and Tyr-32-altered proteins. These findings suggest that the evolutionary invariance of Lys-32 reflects only small quantitative changes in the binding and reactivity of cytochrome c.
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PMID:Replacements of lysine 32 in yeast cytochrome c. Effects on the binding and reactivity with physiological partners. 284 32


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