Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using gel filtration chromatography, we find a single peak of deoxythymidine phosphorylating activity in Chlamydomonas reinhardti. This activity has characteristics of a thymidine kinase, in that (1) it will utilize ATP (or dATP) or CTP (or dCTP) as phosphoryl donor, but not AMP or phenyl phosphate, and (2) it is inhibited by dTTP (and less so by dTDP, dUTP, and dUDP) but is unaffected by 3'-5' cyclic AMP. Partially purified chlamydomonas thymidine kinase has a pH optimum near 8.5, and a molecular weight of 80,000 to 85,000 daltons. Kinetic studies indicate a ping-pong mechanism with a Km for thymidine of 1.5 x 10(-7) moles per liter. 5-Bromo- and 5-fluorodeoxyuridine, and to a lesser degree deoxyuridine, are competitive inhibitors, but significant phosphorylation of these nucleotides could not be demonstrated in vitro by thymidine kinase. While thymidine is phosphorylated to dTMP by crude Chlamydomonas extracts, greater than 80% of the product formed by the partially purified enzyme is dTTP. Further, the gel filtration elution position of the single deoxythymidylate kinase activity present in cell extracts coincides with that of thymidine kinase. These results suggest that a multifunctional enzyme, rather than three separate phosphorylating activities, may be responsible for dTTP formation.
Mol Gen Genet 1979 Nov
PMID:Characterization of thymidine kinase and phosphorylation of deoxyribonucleosides in Chlamydomonas reinhardti. 4 38

Compound Hoe 15,030 is an analogue of berenil which is as effective as berenil in inducing petite mutants in Saccharomyces cerevisiae. Hoe 15,030 has greater stability than berenil in aqueous solution, and is less toxic to yeast at high drug concentrations. Mutants of S. cerevisiae strain J69-1B have been isolated which are resistant to the petite inducing effects of Hoe 15,030. Three mutant strains (HR7, HR8 and HR10) were characterized and each was shown to carry a recessive nuclear mutation determining resistance to Hoe 15,030. The degree of resistance to Hoe 15,030 is different for each mutant, and each was found to be co-ordinately cross-resistant both to berenil and to another analogue of berenil, Hoe 13,548. However, the three mutants show no cross-resistance to other unrelated petite inducing drugs, including ethidium bromide, euflavine and 1-methyl phenyl neutral red. Further studies on the mutants revealed that each strain exhibits characteristic new properties indicative of changes in mitochondrial membrane functions concerned with the replication (and probably also repair) of mitochondrial DNA. Thus, mutant HR7 is hypersensitive to petite induction by the detergent sodium dodecyl sulphate under conditions where the parent J69-1B is unaffected by this agent. Mutant HR8 is even more sensitive to sodium dodecyl sulphate than is HR7, and additionally shows a markedly elevated spontaneous petite frequency. Isolated mitochondria from strains HR8 and HR10 (but not HR7) show resistance to the inhibitory effects of Hoe 15,030 on the replication of mitochondrial DNA in vitro.
Mol Gen Genet 1979
PMID:Studies on the induction of petite mutants in yeast by analogues of berenil. Characterization of three mutants resistant to the compound Hoe 15,030. 4 9

The nuclear pleiotropic respiratory-deficient mutant pet1 (previously M126) exhibits cytochromes aa3 and b deficiencies accompanied by loss of the oligomycin-sensitivity of the mitochondrial ATPase. The mutant pet1, unable to grow on glycerol, growth on glucose. The latter phenotypic trait symbolized by ANAS-D, exhibits a high frequency (2 to 4 X 10(5)) Of spontaneous suppression into Antimycin A-resistant strains. Mutagenesis with MnCl2 increases by a factor of 10(2) the frequency of ANAR-D derivatives. This suppression is partial since none of the suppressed strains is able to grow on glycerol even when respiratory functions and cytochromes activities are restored as in the pet1 [SUP2] strain. In the latter strain it is concluded that the extralocus suppressor gene [SUP2] is responsible for the ANAR-D trait. Tetrad analysis in a cross homozygous for pet1 demonstrates a non-Mendelian segregation pattern for the SUP2 suppressor gene. In stable diploids, homozygous for pet1, the [SUP2] suppressor exhibits a mitotic segregation pattern. Furthermore the transmission of the [SUP2] gene is decreased by ethidium bromide treatment. Therefore, the [SUP2] suppressor gene responsible for partial suppression of the nuclear pleiotropic phenotype in mutant pet1 is of cytoplasmic heredity.
Mol Gen Genet 1976 Nov 24
PMID:A cytoplasmic gene for partial suppression of a nuclear pleiotropic respiratory deficient mutant in the petite negative yeast Schizosaccharomyces pombe. 13 78

Some physiological properties of a multiple-drug-resistant mutant with a permeability barrier to chloramphenicol and its isogenic parental strain were compared. The ATPase specific activity of plasma and mitochondrial membranes isolated from the mutant strain was approximately 20% lower (P less than 0.001, Tables 1 and 2) than that of membranes isolated from the isogenic parental strain. Additional evidence of altered mitochondrial function was: (i) the enhanced growth of the parental strain was eliminted by the [rho-] state (Table 3); (ii) the mutant strain had a greater resistance to petite induction by ethidium bromide (Table 4); (iii) the mutant strain was unable to use a nonfermentable energy source for respiratory adaptation (Table 5). It is proposed that a single gene mutation has resulted in an alteration of some physiological properties of the plasma and mitochondrial membranes.
Mol Gen Genet 1977 Mar 28
PMID:Single gene alteration of plasma and mitochondrial membrane function in Saccharomyces cerevisiae. 14 Oct 2

The molecule of type I collagen from skin consists of two alpha1(I)-chains and one alpha2-chain. The sequence of the entire alpha1-chain comprising 1052 residues is summarily presented and discussed. Apart from the 279 residues of alpha1(I)-CB8 whose sequence has been established for rat skin collagen, all sequences have been determined for calf skin collagen. In order to facilitate sequence analysis, the alpha1-chain was cleaved into defined fragments by cyanogen bromide or hydroxylamine or limited collagenase digestion. Most of the sequence was established by automated stepwise Edman degradation. The alpha1-chain contains two basically different types of sequences: the triple helical region of 1011 amino acid residues in which every third position is occupied by glycine and the N- and C-terminal regions not displaying this type of regularity. Both of these non-triple helical regions carry oxidizable lysine or hydroxylysine residues as functional sites for the intermolecular crosslink formation. Implications of the amino acid sequence for the stability of the triple helix and the fibril as well as for formation of crosslinks are discussed. Evaluation of the sequence in connection with electron microscopical investigations yielded the parameters of the axial arrangement of the molecules within the fibrils. Axial stagger of the molecules by a distance D = 670 angstrom = 233 amino acid residues results in maximal interaction of polar sequence regions of adjacent molecules and similarly of regions of hydrophobic residues. Ordered aggregation of molecules into fibrils is, therefore, regulated by electrostatic and electrophobic forces. Possible loci of intermolecular crosslinks between the alpha1-chains of adjacent molecules may be deduced from the dimensions of the axial aggregation of molecules.
Mol Cell Biochem 1975 Sep 30
PMID:Information contained in the amino acid sequence of the alpha1(I)-chain of collagen and its consequences upon the formation of the triple helix, of fibrils and crosslinks. 17 54

A noncovalent complex of the apoprotein (1-104) and cyanogen bromide heme fragment containing residues 1 to 65, (1-65) H, has been prepared from horse heart cytochrome c. Conditions under which the redundant portions of the ferrous complex can be removed by limited trypsin digestion have been devised. The complementing fragments have been isolated from the derived complexes and four apofragments and one heme fragment have been identified in the amino acid sequence of cytochrome c. They are (39-104), (40-104), (54-104), (56-104), and (1-53)H. The formation of an ordered ferric complex composed of one heme fragment and one apofragment for the cases (1-53)H (39-104), (1-53)H-(40-104), (1-53)H-(54-104), and (1-53)H-(56-104) has been demonstrated by the quenching of the tryptophan 59 fluorescence and the regain of biological activity in a cytochrome b2 assay. The apparent dissociation constant has been estimated as less than 3 X 10(-7) M in all the aforementioned cases. Thus, the region (between residues 38 and 57) of the amino acid sequence permissible for cleavage without disruption of the ordered structure indicated by the present in vitro experiments corresponds to that (between residues 38 and 57) evolutionally deleted in the three-dimensional structure of Pseudomonas aeruginosa cytochrome c551 discovered by Dickerson et al. (Dickerson, R.E., Timkovich, R., and Almassy, R.J. (1976) J. Mol. Biol. 100, 473-491).
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PMID:Formation of a biologically active, ordered complex from two overlapping fragments of cytochrome c. 19 Feb 31

By equilibrium ultracentrifugation and electrophoresis in agarose gel data were obtained on the binding of [3H]cyclic adenosine monophosphate ([3H]cAMP) to the transcriptional complex of mitochondria with the density 1.825 g/ml in CsCl ethydium bromide. Treatment of the complex with RNase, DNase and pronase change the density of [3H]cAMP bound material; rifampicin prevents detection of [3H]cAMP. Study of inner membrane lysates showed that [3H]cAMP is bound to structures active in RNA and protein synthesis in mitochondria. The conclusion is made that cAMP is involved in formation of the transcriptional complex much as it is involved in initiation of transcription in bacterial operons.
Mol Cell Biochem 1977 Feb 04
PMID:Detection of [3H]cyclic AMP in the transcription complex of rat liver mitochondria. 19 94

The interactions between the mitochondrial and nucleocytoplasmic systems required for mitochondriogenesis have been investigated at several different levels. Those involved in the formation of functional enzyme complexes have been studied using cytochrome oxidase: this multimeric (2 X 7 and 2 X 6 subunits for enzymes from yeast and beef heart respectively) has been resolved, and the mitochondrial contribution has been shown to be dispensible for catalytic function proper. Using novel mutants, with a mitochondrial mode of inheritance, a mitochondrial gene product localized in the oligomycin-sensitive ATPase has been implicated in the assembly not only of this complex, but of cytochrome oxidase as well. Interactions required for the genetic competence of the mitochondrial system have become apparent as a result of studies in the mechanism of action of the highly effective mitochondrial mutagen ethidium bromide. This agent first becomes covalently inserted into mitochondrial DNA and, after its excision, eventually results in extensive degradation of the macromolecule. The excision reaction has now been shown to be performed by a complex between the oligomycin-sensitive ATPase and a DNA-binding protein presumably involved in recognizing the damage. On the level of replication and expression of the mitochondrial genome studies using thermolabile mutants have demonstrated that these processes appear independent of the replication of nuclear DNA but not of its expression.
Mol Cell Biochem 1977 Feb 04
PMID:Integration and regulation of mitochondrial assembly in yeast. 19 97

The binding of ethidium bromide and acriflavin dyes with DNA modified with a spin-labelled analogue of ethylene imine has been studied. These spin-labels were shown to bind covalently to DNA, at the same time the number of the dye molecules bound is decreased without any changes in the binding constant. Analysis of ESR spectra of the samples in the frozen 50% water-glycerol solution at 77 degrees K for spin-labelled DNA has shown that addition of the dyes increases distance between the labels. This fact might be explained by an increase in DNA length upon formation of the complex with dye molecules.
Mol Biol (Mosk)
PMID:[Study of DNA-dye interaction by spin-labels]. 22 30

We have evaluated the sugar pucker geometry at the intercalation site of propidium diiodide into the self-complementary dinucleoside monophosphate duplexes cytidylylguanosine and deoxycytidylyldeoxyguanosine as a function of the nucleotide/drug ratio in aqueous solution. Our solution results support the observation by Sobell and coworkers [Sobell, H.M., Tsai, C.C., Jain, S.C. & Gilbert, S.G. (1977) J. Mol. Biol. 114, 333--365] of a C3' endo (3'-5')C2' endo sugar pucker geometry in the 2:2 intercalation complex of ethidium bromide into the iodocytidylylguanosine duplex in the crystalline state. We demonstrate further that the mixed sugar pucker observed for the intercalation of propidium diiodide into the miniature RNA duplex in solution persists in the intercalative complex of this trypanocidal drug into the corresponding miniature DNA duplex in solution.
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PMID:Sugar pucker geometries at the intercalation site of propidium diiodide into miniature RNA and DNA duplexes in solution. 27 25


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