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

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Query: EC:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A lambda gt11 cDNA expression library was screened with antibodies directed against individual subunits of complex I from Neurospora crassa. Clones encoding cytoplasmically synthesized polypeptides with apparent molecular masses of 22, 29, 31, and 33 kDa were isolated. Northern blot analysis revealed that the corresponding genes are transcribed into mRNA species of about 0.85, 0.95, 1.3, and 1.4 kilobases, respectively. Further characterization of clones encoding the 22-kDa subunit was performed. A cDNA insert of 755 base pairs containing the complete coding sequence was used to express the polypeptide in vitro. A precursor of the protein is synthesized on cytoplasmic ribosomes without a cleavable signal sequence. Our data indicate that after import into the organelle and before assembly into complex I, the 22-kDa polypeptide forms intramolecular disulfide bridge(s). Nucleotide sequencing revealed an open reading frame coding for a protein of 183 amino acids. A molecular mass of 20,828 daltons was calculated. The polypeptide is hydrophilic and contains no obvious membrane-spanning domains. Eight cysteine residues arranged in a regular pattern are found in the primary structure of the protein. Therefore, this subunit is a good candidate to bind at least one of the iron-sulfur centers present in complex I of the respiratory chain.
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PMID:Molecular cloning of subunits of complex I from Neurospora crassa. Primary structure and in vitro expression of a 22-kDa polypeptide. 214 43

The primary structure of the 49 K subunit of the respiratory chain NADH:ubiquinone reductase (complex I) from Neurospora crassa was determined by sequencing cDNA, genomic DNA and the N-terminus of the mature protein. The sequence lengths correlate to a molecular mass of 54,002 daltons for the preprotein and 49,239 daltons for the mature protein. The presequence consists of 42 amino acids of typical composition for sequences which target nuclear-encoded proteins into mitochondria. The mature protein consists of 436 amino acids and shows 64% similarity to a 49 K subunit of bovine heart NADH:ubiquinone reductase and 33% to a predicted translation product of an open reading frame in the chloroplast DNAs of Marchantia polymorpha and Nicotiana tabacum. Evidence for an iron-sulfur cluster in the subunit is discussed.
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PMID:The 49 K subunit of NADH: ubiquinone reductase (complex I) from Neurospora crassa mitochondria: primary structure of the gene and the protein. 214 27

Five distinct low potential iron-sulfur clusters have been identified potentiometrically in the membrane particles from Thermus thermophilus HB-8. Three of these clusters (designated as [N-1H]T, [N-2H]T, and [N-3]T) exhibit the following midpoint redox potentials and g values (Em8.0 = -274 mV, gx,y,z = 1.93, 1.94, 2.02), (Em8.0 = -304 mV, gx,y,z = 1.89, 1.95, 2.04), and (Em8.0 = -289 mV, gx,y,z = 1.80, 1.83, 2.06), respectively. These clusters, one binuclear and two tetranuclear, have been shown to be components of the energy coupled NADH-menaquinone oxidoreductase complex (NADH dh I). They are reducible by NADH in the piericidin A-inhibited aerobic membrane particles as well as in the purified NADH dh I complex. Two additional very low potential iron-sulfur clusters (one binuclear, [N-1L]T, and one tetranuclear, [N-2L]T) were observed in membrane particles. These clusters possess the following physiochemical properties (Em8.0 = -418 mV, gx,y,z = 1.93, 19.5, 2.02) and (Em8.0 = -437 mV, gx,y,z = 1.89, 1.95, 2.04), respectively. No high potential tetranuclear cluster equivalent to the mitochondrial iron-sulfur cluster [N-2]B was found in this bacterial system. In membrane particles isolated from T. thermophilus HB-8 cells, four different semiquinone species have been identified based on their redox midpoint potentials [Em9(Q/QH2) = 40, -100, -160, -300 mV] and sensitivity to the quinone analogue inhibitor, 2-heptyl-4-hydroxy quinoline-N-oxide. Of these semiquinone species the -100 mV component has been suggested to be part of the NADH dehydrogenase. Piericidin A sensitive delta psi formation has been demonstrated to be coupled to the NADH-MQ1 oxidoreductase in membrane vesicles of T. thermophilus HB-8.
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PMID:Studies on the NADH-menaquinone oxidoreductase segment of the respiratory chain in Thermus thermophilus HB-8. 215 29

Several NAD(P)H-dependent ferri-reductase activities were detected in sub-cellular extracts of the yeast Saccharomyces cerevisiae. Some were induced in cells grown under iron-deficient conditions. At least two cytosolic iron-reducing enzymes having different substrate specificities could contribute to iron assimilation in vivo. One enzyme was purified to homogeneity: it is a flavoprotein (FAD) of 40 kDa that uses NADPH as electron donor and Fe(III)-EDTA as artificial electron acceptor. Isolated mitochondria reduced a variety of ferric chelates, probably via an 'external' NADH dehydrogenase, but not the siderophore ferrioxamine B. A plasma membrane-bound ferri-reductase system functioning with NADPH as electron donor and FMN as prosthetic group was purified 100-fold from isolated plasma membranes. This system may be involved in the reductive uptake of iron in vivo.
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PMID:Iron-reductases in the yeast Saccharomyces cerevisiae. 218 97

A catalytic component of the bovine mitochondrial NADH:ubiquinone oxidoreductase complex (Complex I) is a soluble NADH dehydrogenase iron-sulfur flavoprotein (FP). FP is composed of three subunits of Mr 51,000, 24,000, and 9,000, and contains FMN and two iron-sulfur clusters. Previous studies by others with the use of various chemical probes had suggested that, except for an access for NADH to the 51-kDa subunit, the FP polypeptides are buried within Complex I and shielded from the medium. In the present study, monospecific antibodies were raised to each of the three FP subunits, and used in conjunction with Complex I, submitochondrial particles (SMP), mitoplasts, and intact mitochondria as sources of antigens. Results of enzyme-linked immunosorbent assays and 125I-protein A labeling experiments indicated that epitopes from the 51-, 24-, and 9-kDa subunits of FP are exposed to the medium in Complex I and SMP, but not in mitoplasts and mitochondria. Appropriate enzymatic assays showed that none of the antibodies inhibited the NADH dehydrogenase activity of isolated FP or the NADH oxidase activity of SMP. These results have been discussed in relation to the structure of Neurospora Complex I deduced from membrane crystals of the isolated enzyme complex by Leonard et al. [K. Leonard, H. Haiker, and H. Weiss (1987) J. Mol. Biol. 194, 277-286].
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PMID:Studies on the structure of NADH:ubiquinone oxidoreductase complex: topography of the subunits of the iron-sulfur flavoprotein component. 246 82

Anti-mitochondrial autoantibodies (AMA) from patients with primary biliary cirrhosis (PBC) were analysed for fine specificity by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Inhibition ELISA showed that complex I (NADH-ubiquinone reductase) from beef heart mitochondria completely inhibited the binding of AMA to mitochondrial inner membranes (SMP), indicating that the major mitochondrial antigens are located in complex I. Immunoblot analysis of beef heart SMP, complex I and the iron sulphur (IP) subfraction of complex I revealed several antigens, one of which (75 kDa) reacted with all PBC sera but not with the additional autoimmune sera tested. Resolution of SMP or complex I by two-dimensional electrophoresis yielded in both preparations a polypeptide of 75 kDa with an isoelectric point of 6.4, which reacted with PBC serum and with rabbit antisera raised against the 75,000 subunit of complex I. In immunoblot experiments, the antigenicity of the 75,000 polypeptide in SMP, complex I, and the IP subfraction is increased by prior reduction of the sample with mercaptoethanol. This suggests a similarity to the PBC-specific 'M-2' antigen, which is also sensitive to sulphur reagents. The data indicate that the 75 kDa polypeptide of complex I is a major mitochondrial antigen binding AMA in PBC sera, and allows us to identify the location and probable function of the PBC antigen.
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PMID:Mitochondrial autoantigens in primary biliary cirrhosis. Association of disease-specific determinants with a subunit of complex I (NADH-ubiquinone reductase) of the inner mitochondrial membrane. 246 24

To investigate the molecular abnormality in the mitochondria from various tissues of an autopsied patient exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, we have examined the enzymatic activity, iron-sulfur cluster, and subunit composition of the NADH-ubiquinone oxidoreductase (complex I). Rotenone-sensitive NADH-cytochrome c reductase activity was found to be decreased in all the tissues examined. A detailed study of the liver mitochondria has shown that NADH-ubiquinone oxidoreductase activity was greatly diminished. Analysis of the electron paramagnetic resonance spectra of the liver submitochondrial particles revealed a disproportionate deficiency of iron-sulfur clusters in the complex I segment of the respiratory chain. Signals from the clusters N-2 and N-3 diminished more drastically than those from clusters N-1b and N-4. Immunoblotting analysis showed that the 75-kD, 51-kD, and several other subunits were markedly diminished among multiple subunit polypeptides of complex I. These findings suggest that the underlying bases for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are defects, at least, in the complex I subunits containing a flavin and/or iron-sulfur cluster(s), which resulted in deficiencies of some iron-sulfur clusters.
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PMID:Disproportionate deficiency of iron-sulfur clusters and subunits of complex I in mitochondrial encephalomyopathy. 249 47

Capsaicin and its analogs with different acyl moieties were found to inhibit the electron-transfer activity of NADH-coenzyme Q oxidoreductase isolated from beef heart mitochondria. The inhibitory potency of capsaicin was lower than those of dihydrocapsaicin and analogs with heptanoyl, capryl, undecanoyl, and lauroyl moieties, but was higher than those of analogs with palmitoyl and stearoyl moieties. The analog with the lauroyl moiety showed the strongest inhibition. These results suggest that hydrophobicity and the appropriate carbon chain length of the acyl moiety are important for the binding of compounds to the enzyme. On the other hand, capsaicin and its analogs did not interrupt rotenone-insensitive electron transfer from NADH to menadione. Furthermore, these compounds had almost no effect on the spectral properties and EPR signals arising from iron-sulfur clusters of the NADH-treated enzyme. Kinetic analyses with double-reciprocal plots showed that these compounds were competitive inhibitors with respect to coenzyme Q1, an electron acceptor. These results strongly suggest that capsaicin and its analogs bind to the coenzyme Q1 binding site of the enzyme.
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PMID:Capsaicin and its analogs inhibit the activity of NADH-coenzyme Q oxidoreductase of the mitochondrial respiratory chain. 249 67

The mitochondrial NADH-ubiquinone reductase (complex I) is an assembly of approximately 26 different polypeptides. In vertebrates and invertebrates, seven of its subunits are the products of genes in the mitochondrial DNA, and homologues of these genes have been found previously in the chloroplast genomes of Marchantia polymorpha and Nicotiana tabacum, although their function in the chloroplast is unknown. The remainder of the subunits of the mitochondrial complex are nuclear gene products that are imported into the organelle, amongst them the 49 kd subunit, a component of the iron--sulphur subcomplex of the enzyme. In the present work, the N-terminal sequence of this protein has been determined, and this has been used to design two mixtures of synthetic oligonucleotides, each containing 32 different sequences 17 bases long. These mixtures have been used as hybridization probes to isolate cDNA clones from a bovine library. The DNA sequences of these clones have been determined and they encode the mature 49 kd protein, with the exception of amino acids 1 and 2. The protein sequence of 430 amino acids is closely related to those of proteins that are encoded in open reading frames (ORFs) present in the chloroplast genomes of M.polymorpha and N.tabacum. Only one cysteine is conserved and the sequences provide no indication that the 49 kd protein contains iron--sulphur centres. These ORFs are found in the single copy regions of chloroplast DNA in close proximity to four of the homologues of the mammalian mitochondrial genes that encode subunits of complex I.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A homologue of the nuclear coded 49 kd subunit of bovine mitochondrial NADH-ubiquinone reductase is coded in chloroplast DNA. 249 81

The 24-kDa subunit of mitochondrial NADH-ubiquinone reductase (complex I) is an iron-sulfur protein that is present in the flavoprotein or NADH dehydrogenase II subcomplex. It is a nuclear gene product and is imported into the organelle. A group of human patients with mitochondrial myopathy have been shown to have reduced levels of subunits of complex I in skeletal muscle mitochondria, and in one patient the 24-kDa subunit appears to be absent (Schapira et al., 1988). To investigate the genetic basis of this type of myopathy, cDNA clones have been isolated from a bovine library derived from heart and liver mRNA by hybridization with two mixtures of 48 synthetic oligonucleotides 17 bases in length that were designed on the basis of known protein sequences. The recombinant DNA sequence has been determined, and it encodes a precursor of the mature 24-kDa protein. The N terminus of the mature protein is preceded by a presequence of 32 amino acids that has properties that are characteristic of mitochondrial import sequences. The sequence of the mature protein deduced from the cDNA contains a segment of nine amino acids that was not determined in an earlier partial protein sequence analysis. The bovine clone has been employed as a hybridization probe to identify cDNA clones of the human homologue of the 24-kDa protein. Its DNA sequence has also been determined, and it codes for a protein that is closely related to the bovine protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of import precursors of the bovine and human 24-kDa subunit. 250 Sep 70


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