Disease relevance of Manganese cation

• Trace amounts of Mn(2+) potently inhibit Ty1 RT and HIV-1 RT in vitro when the preferred cation, Mg(2+), is present [1].
• Human Pol mu, overproduced in Escherichia coli in a soluble form and purified to homogeneity, displays intrinsic terminal deoxynucleotidyltransferase activity and a strong preference for activating Mn(2+) ions [2].
• To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg(2+) or Mn(2+) [3].
• We extend our hypothesis here to include consideration of respiration, tricarboxylic acid cycle activity, peptide transport and metal reduction, which together with Mn(II) transport represent potential new targets to control recovery from radiation injury [4].
• Three classes of mutants were found: mutants indistinguishable from wild type (Class 1), mutants indistinguishable from the pmr1 null strain (Class 2), and mutants with differential sensitivity to BAPTA and Mn(2+) toxicity (Class 3) [5].

Psychiatry related information on Manganese cation

• Nuclear magnetic resonance relaxation time studies on the manganese(II) ion complex with succinyl coenzyme A synthetase from Escherichia coli [6].
• On the basis of the obtained activation parameters, the exchange mechanism of the studied seven-coordinate manganese(II) complexes follows a dissociative pathway (Id mechanism) [7].

High impact information on Manganese cation

• A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally remove these radicals [8].
• Cytoplasmic accumulation of Mn(2+) in pmr1 cells may directly affect reverse transcriptase (RT) activity [1].
• The transposition defect results from Mn(2+) accumulation that inhibits reverse transcription [1].
• Phagosomes from Nramp1(+/+) mice extrude Mn(2+) faster than their Nramp(-/-) counterparts [9].
• EAC RNA polymerases Ia, Ib, IIa, and IIb possessed Mg2+ ion, Mn2+ ion, and (NH4)2 SO4 optima, molecular weights, and thermal sensitivities similar to those reported for other mammalian DNA-dependent RNA polymerases [10].

Chemical compound and disease context of Manganese cation

• Here, we describe the effects of Zn(2+) on complex I to define whether complex I may contribute to mediating the pathological effects of zinc in states such as ischemia and to determine how Zn(2+) can be used to probe the mechanism of complex I. Zn(2+) inhibits complex I more strongly than Mg(2+), Ca(2+), Ba(2+), and Mn(2+) to Cu(2+) or Cd(2+) [11].
• Similarly, the binding of Mn-dATP to DNA polymerase I increased the distances from Mn(II) to the H2, H8, H'1, and H'4 protons of dATP but the adenine-deoxyribose torsion angle of 90 degrees was preserved [12].
• Amyl acetate exposure increased augmentation of Mn(2+) uptake in olfactory epithelium on the open side in control group but the augmentation was decreased after hypoxia [13].
• We report that the overexpressed ACMSD enzyme from Pseudomonas fluorescens requires a divalent metal, such as Co(II), Fe(II), Cd(II), or Mn(II), for catalytic activity and that neither a redox reagent nor an organic cofactor is required for the catalytic function [14].
• On the basis of similarities to the six-line spectrum observed for the azide-complexed E. coli manganese superoxide dismutase, the newly detected six-line spectrum was assigned to a hexacoordinate Mn(II) center resulting from the coordination of a nearby water molecule to the normally five-coordinate center [15].

Biological context of Manganese cation

• The structuring of a 13 residue loop, resulting from UDP-GlcNAc/Mn(2+) binding, provides an explanation for the ordered sequential 'Bi Bi' kinetics shown by GnT I [16].
• The yeast Saccharomyces cerevisiae expressing a cDNA library prepared from Stylosanthes hamata was screened for enhanced Mn(2+) tolerance [17].
• Together, our results establish that Pmr1-dependent Ca(2+) and/or Mn(2+) ion homeostasis is necessary for TOR signaling [18].
• Based on these data, we propose that TroR represents a unique regulatory system for controlling gene expression in T. pallidum in response to Mn(2+) [19].
• In the course of studies to test the antioxidant activity of Mn(II) on HeLa cells, it was observed at high concentrations (1-2 mM) that Mn(II) also induced apoptosis, as judged by changes in cell morphology, caspase-3 activation, cleavage of poly(ADP) ribose, and DNA condensation [20].

Anatomical context of Manganese cation

• Quenching of the probe by Mn(2+) was used to monitor the flux of divalent cations across the phagosomal membrane in peritoneal macrophages obtained from Nramp1-expressing (+/+) and Nramp1-deficient (-/-) macrophages [9].
• We suggest that the ShMTP1 proteins are members of the CDF family involved in conferring Mn(2+) tolerance and that at least one of these proteins (ShMTP1) confers tolerance by sequestering Mn(2+) into internal organelles [17].
• These and other measurements show that treatment with Mn(II) leads to enhancement of the mitochondrial "membrane mass," has no effect on mitochondrial volume, and does not affect the permeability transition pore [20].
• Integrin alpha(4)beta(7) mediates rolling adhesion in Ca(2+) and Ca(2+) + Mg(2+), and firm adhesion in Mg(2+) and Mn(2+), mimicking the two key steps in leukocyte accumulation in inflamed vasculature [21].
• Both extracellular application of Mn(2+) (at micromolar concentrations) and viral-mediated neuronal expression of a constitutively active form of the ras-related GTPase R-ras (R-ras(38V)) potently promoted late-embryonic retinal neurite outgrowth on LN-1 substrata [22].

Associations of Manganese cation with other chemical compounds

• Instead, manganese oxalate worked as a diffusible redox shuttle, first being oxidized from Mn(II) to Mn(III) by a peroxidase and then being reduced to Mn(II) by a simultaneous oxidation of the lignin monomers to radicals that formed covalent linkages of the lignin type [23].
• A Mn(2+), with octahedral geometry, is positioned between the alpha and beta phosphates acting in concert with the Zn(2+) to align and polarize the substrate for catalysis [24].
• It is presumed that the redox potential of the Mn(II) in equilibrium with Mn(III) couple in such a complex permits H2O2 to carry out facile reactions with Mn(II) comparable to those that occur with Fe(III) and Cu(II) chelate complexes, in which OH. and O2-. are established intermediates [25].
• The structure of the variant has been determined by x-ray crystallography to define the coordination environment of bound Mn(2+) and Cd(2+) [26].
• The decrease in amplitude of the electron spin resonance spectrum of the cysteine-bound spin-label, 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidinoxyl, brought about by the magnetic interaction with tightly bound manganous ion, was used as a probe of conformational change in actin on binding myosin [27].

Gene context of Manganese cation

• Adhesion to SAA was further enhanced by Mn(2+) and the physiological agonist, thrombin [28].
• C. elegans PMR1 overexpressed in COS-1 cells transports Ca(2+) and Mn(2+) with high affinity into the Golgi apparatus in a thapsigargin-insensitive manner [29].
• The subdomain analysis of CAX2-C identified a 3-amino acid region that is responsible for Mn(2+) specificity of CAX2 [30].
• Further studies using point-mutated SULT1A3s mutated at amino acid residues in these two regions and deletional mutants missing residues 84-86 and 84-90 implicate residue Glu-146 (in variable Region II of SULT1A3), as well as the presence of residues 84-90 of variable Region I, in the stereospecificity in the absence of Mn(2+) [31].
• Using several different criteria we demonstrated that CCC1 encodes a transporter that effects the accumulation of iron and Mn(2+) in vacuoles [32].

Analytical, diagnostic and therapeutic context of Manganese cation

• To examine the structural identities of reactive free radicals and the mechanism of the oxidative modification of proteins, we used EPR and spin-trapping methods to investigate the oxidation of amino acids by H2O2 as well as the decomposition of H2O2 itself catalyzed by Mn(II) ions [33].
• Titration of the binary enzyme-Mn(II) complex with CrATP decreases the characteristic enhancement due to Mn(II) from 24 +/- 3 to 6 +/- 1 [34].
• Following gel filtration chromatography on Sephacryl S-200 in the presence of Mn(2+), PP1(C) coeluted with I(1)(PP2A) and I(2)(PP2A) in the void volume [35].
• Mutational analyses of the presumptive metal ion-binding ligands (Asp(122), Asp(222), and Glu(220)) together with immunoprecipitation assays provided compelling evidence to link both the Mg(2+)- and Mn(2+) and ATP-dependent endonuclease activities to PI-MtuI [36].
• Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+) [37].

References