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

Metal ions are crucial trace elements for bacteria infecting the human host. The LraI (lipoprotein receptor-associated antigen I) transporter in Streptococcus spp. belongs to the superfamily of ABC transporters. The transporter consists of a lipoprotein, an ATP-binding protein and a hydrophobic integral membrane protein. Here, we describe a new member of the LraI family in the important human pathogen Streptococcus pyogenes. The system was identified in silico by analysis of the S. pyogenes Genome Sequencing Project. The S. pyogenes operon exhibits an atypical organization compared with equivalents in other Streptococcus spp. The presence and atypical organization of the operon was verified in a number of S. pyogenes strains of different serotypes. Transcriptional analysis of the LraI operon demonstrates a polycistronic transcription attenuated by a stable stem-loop structure, which allows the lipoprotein to be expressed in larger quantities than the other two components. The localization of the native lipoprotein at the bacterial surface was shown by proteolytic digestion of S. pyogenes bacteria and NH2-terminal sequencing of a released lipoprotein fragment. Recombinant lipoprotein was expressed as a GST fusion protein, and studies of molecular interactions with metal radioisotopes demonstrated that the protein has affinity for Zn(II), Fe(III) and Cu(II). Zn(II) and Cu(II) were found to compete for the same binding site, whereas Fe(III) uses a second site. Also, proton-induced X-ray analysis of lipoprotein samples identified iron, copper and zinc. Finally, a mutant strain lacking a functional mtsABC operon was generated and showed reduced uptake of 55Fe and 65Zn compared with the wild-type strain. The operon encoding this novel ABC transporter with multiple specificity for metal cations is designated mtsABC, for metal transporter of Streptococcus.
Mol Microbiol 1999 Nov
PMID:Identification and characterization of a Streptococcus pyogenes ABC transporter with multiple specificity for metal cations. 1056

In this study we report a spectroscopic investigation on the structure and stability of Cu(II)-complexes that are formed in a minimum growth medium (MM), normally used for Bacillus subtilis cultures. As other transition metals, Cu(II) compounds are toxic to this bacterium and the toxicity depends on the Cu(II) concentration. MM contained NH4+ ions and asparagine (asn) as the source of inorganic and organic nitrogen. Both ESR and electronic spectra demonstrated the very important role played by the amino acid asparagine in the coordinative behaviour of Cu(II). In particular, three different complexes were evidenced: Cu(H2O)6(2+); Cu(asn)+ and Cu(asn)2. The relative amount of these three species strongly depended on pH, on Cu:asn ratio and on the presence of the phosphate ions. They were identified and evaluated quantitatively by extensive simulation of the electron spin resonance (ESR) spectra recorded in different experimental conditions. The bis-complex was found to be more stable in MM than in an asparagine-containing water solution with the same Cu:asn ratio. A comparison of the spectroscopic results with microbiological investigations is also made.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Feb 01
PMID:Cu(II) complexes in bacterial growth medium: electron spin resonance study. 1072 51

Quantitative EPR method was applied to characterise four types of humic acids (HA) derived from composts, soil, peat and soft brown coal. For each sample of HA the level of native (indigenous) radicals was estimated. Interactions of the HA with various gaseous agents and organic solvents were investigated. Strong effects of gaseous ammonia and aliphatic amines on spin concentration enhancement were observed; additionally, higher values of g-value were found to be associated with the formed 'transient' radicals. Correlation of copper(II) ions uptake by different HA with effect diminishing primary spin concentration was established. It was recognised that the radical centres, which are enhanced by 'ammonia effect' are quenched in the formed HA-Cu(II) complexes. The both opposite effects are competitive from each other, where 'copper(II) quenching effect' prevails. Reaction of nitrogen dioxide with the humic acids was also examined. The presence of diketones and/or other compounds with active methylene group results in formation of the iminoxy radicals; these radicals are immobilized in the solid (macromolecular) matrix of the humic acids.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Feb 01
PMID:Electron paramagnetic resonance (EPR) studies on stable and transient radicals in humic acids from compost, soil, peat and brown coal. 1072 56

The complexes of adriamycin (ADM) with Cu(II) and Fe(II) have been studied by visible absorption, circular dichroism (CD) and fluorescence spectra, respectively. In Tris buffer at pH 7.0, either metal ions forms a single species with adriamycin: Cu(ADM)2 or Fe(ADM)3. Interaction of these two complexes with various biological molecules has been examined. It is shown that some amino acids, glutathione and albumin are able to remove the Cu(II) ion from Cu(II)-ADM complex, releasing the free drug. However, Fe(II)-ADM keeps in an undissociated form under the same conditions. The possibility of Fe(II) ADM as a new alternative drug has been discussed.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Feb 15
PMID:Spectroscopic studies of copper(II) and iron(II) complexes of adriamycin. 1079 73

Complexing of 3,5-di-tert-butyl-1,2-benzoquinone-2-monooxime with Cu(II) in air and under N2 gave Cu(qo)2 and Cu(qo)2 x H2O (where qo is 3,5-di-tert-butyl-1,2-benzoquinone-2-monooximato-anion) complexes, respectively. The ESR spectroscopy showed that the reduction of these complexes with P(PhX)3 (X = H, m-Cl, m-CH3, p-Et2N-) and 1,4-bis(diphenyldiphosphino) butane (dppb) proceeds via the radical formation (phenoxazine, amino phenoxy and nitrene type radical intermediates) and pathways of reduction depend on the structure of these complexes. The reaction of Cu(qo), with dppb and P(PhX)3 phosphines gave essentially identical ESR spectra. At the same time, reduction of Cu(qo)2 x H2O with PPh3 result in entirely different unstable radical spectrum (g = 2.0046) which is further converted to another relatively stable Cu-containing radical signal (g = 2.0052). The unstable radical species attributed to nitrene type radicals. The initial complexes and all radical products were characterized by their ESR and optical spectra.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Apr
PMID:Synthesis and ESR studies of redox reactivity of bis (3,5-di-tert-butyl-1,2-benzoquinone-2-monooximato)Cu(II). 1080 59

We have studied the metal-catalyzed oxidation (MCO) of brain-derived neurotrophic factor (BDNF) with regard to target sites and potential conformational changes of the protein. The exposure of BDNF to three different levels of ascorbate/Cu(II)/O2 [20 microM Cu(II), 2 mM ascorbate (level 1); 20 microM Cu(II), 4 mM ascorbate (level 2); 40 microM Cu(II), 4 mM ascorbate (level 3)], chosen based on the extent of chemical modification of Met and His, respectively, resulted in the exclusive oxidation of a buried Met residue, Met92, at level 1 but in the predominant oxidation of His at level 3. His modification had a significant impact on the structure of BDNF, as quantified by CD and ANSA fluorescence measurements, while Met oxidation had not, also assessed through complementary oxidation of BDNF through hydrogen peroxide. Our ultimate objective was the correlation of the surface exposure of an oxidized His residue in a protein with potential effects on the conformational integrity of the oxidized protein. In a series of three proteins, human growth hormone (hGH), human relaxin (hR1x), and BDNF, we have now observed that His oxidation is paralleled by significant conformational changes when the target His residue is more surface exposed (hR1x, BDNF) while conformational consequences of His modification are less significant when the target His residues are more buried in the interior of the protein (hGH).
Cell Mol Biol (Noisy-le-grand) 2000 May
PMID:Metal-catalyzed oxidation of brain-derived neurotrophic factor (BDNF): selectivity and conformational consequences of histidine modification. 1087 55

Abeta derived from amyloid plaques of Alzheimer's disease-affected brain contain several oxidative posttranslational modifications. In this study we have characterized the amino acid content of human amyloid-derived Abeta and compared it with that of human synthetic Abeta subjected to metal-catalyzed oxidation. Human amyloid derived Abeta has an increased content of arginine (46%) and glutamate/glutamine residues (28%), but a decreased content of histidine residues (-32%) as compared to the expected amino acid content. Incubation of synthetic human Abeta with Cu(II), but not Fe(III), in the presence of H2O2 similarly induced a decrease in histidine residues (-79%), but also a decrease in tyrosine residues (-28%). Our results suggest that histidine and tyrosine are most vulnerable to metal mediated oxidative attack, consistent with our earlier findings that Cu coordinated via histidine residues is redox competent. Our results suggest that the loss of histidine residues in human amyloid-derived Abeta may be a result of Cu oxidation, and that unidentified post-translational mechanisms operate to modify other amino acids of Abeta in vivo.
Cell Mol Biol (Noisy-le-grand) 2000 Jun
PMID:Copper catalyzed oxidation of Alzheimer Abeta. 1087 39

The complexes of 2-thiobarbituric acid with Fe(II), Fe(III), Co(II), Cu(II), Zn(II) and Cd(II) have been isolated and characterized on the basis of elemental analyses, molar conductance, magnetic moment and spectral studies. The thermal decomposition of the metal complexes was studied by TG and DTA techniques. The kinetic parameters namely, activation energy, entropy of activation and the reaction orders were estimated.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Jun
PMID:Spectral and thermal studies of thiobarbituric acid complexes. 1088 28

Free hydroxyl radicals (free (.)OH), singlet oxygen ((1)O(2)), or (. )OH produced by DNA-copper-hydroperoxo complexes are possible DNA-damaging reactive oxygen species (ROS) in the reaction system containing copper, catechol, and DNA. para-Chlorobenzoic acid (pCBA) degradation studies revealed that CuCl(2) mixed with catechol produced free (.)OH. In the presence of DNA, however, inhibition of the pCBA degradation suggested that another ROS is responsible for the DNA degradation. Of a series of ROS scavengers investigated, only KI, NaN(3), and Na-formate-all of the salts tested-strongly inhibited the DNA degradation, suggesting that the ionic strength rather than the reactivity of the individual scavengers could be responsible for the observed inhibition. The ionic strength effect was confirmed by increasing the concentration of phosphate buffer, which is a poor (.)OH scavenger, and was interpreted as the result of destabilization of DNA-copper-hydroperoxo complexes. Piperidine-labile site patterns in DNA degraded by copper and catechol showed that the mixture of Cu(II) and catechol degrades DNA via the intermediate formation of a DNA-copper-hydroperoxo complex. Replacement of guanine by 7-deazaguanine did not retard the DNA degradation, suggesting that the DNA-copper-hydroperoxo complexes do not bind to the guanine N-7 as proposed in the literature.
Environ Mol Mutagen 2000
PMID:DNA degradation by the mixture of copper and catechol is caused by DNA-copper-hydroperoxo complexes, probably DNA-Cu(I)OOH. 1091 54

The structure of the catalytic site in one subunit of bovine CuZn superoxide dismutase is shown to be highly variable. A series of crystal structures at approximately 1.7 A have been determined using data collected from different crystals. Several conformations are observed for the copper site from one of the subunits. These conformations lie between those expected for the Cu(II) and Cu(I) forms of the enzyme and may represent a slow positional rearrangement of the Cu site during the crystallisation process due to the presence of a trace reductant in the mother liquor. These states perhaps indicate some functionally relevant structural steps that ultimately result in the breakage of the imidazolate bridge between the two metal sites. This behaviour is not observed for the second subunit of the dimeric enzyme, which remains in the five-coordinate, distorted square planar geometry in all cases. We suggest that this asymmetric behaviour may be caused by the lack of mobility for the Glu119-Leu142 loop region in the second subunit caused by crystal contacts. This region forms one wall of the active-site cavity, and its mobility has been suggested, via molecular dynamics studies, to be important for the catalytic mechanism.
J Mol Biol 2000 Nov 24
PMID:Conformational variability of the Cu site in one subunit of bovine CuZn superoxide dismutase: the importance of mobility in the Glu119-Leu142 loop region for catalytic function. 1108 Apr 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>