2 research outputs found

    Identification of Unfolding and Dissociation Pathways of Superoxide Dismutase in the Gas Phase by Ion-Mobility Separation and Tandem Mass Spectrometry

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    Cu, Zn-superoxide dismutase (SOD1) is a homodimeric enzyme of approximately 32 kDa. Each monomer contains one Cu<sup>2+</sup> and one Zn<sup>2+</sup> ion, which play catalytic and structural roles in the enzyme. Dimer formation is also essential to its functionality. The spatial structure of this metalloenzyme is also closely related to its bioactivities. Here we investigate the structural and conformational changes of SOD1 in the gas phase by electrospray ionization mass spectrometry (ESI-MS) and ion-mobility (IM) separation combined with tandem mass spectrometry (MS/MS). First, the composition and forms of SOD1 were analyzed by ESI-MS. The dimer, monomer, and apomonomer were observed under different solvent conditions. The dimer was found to be stable, and could retain its native structure in neutral buffer. Ion-mobility separation combined with MS/MS was used to reveal the conformational changes and dissociation process of SOD1 when it was activated in the gas phase. Three different dimeric and two monomeric conformers were observed; three unfolding and dissociation pathways were also identified. The results from this study demonstrate that IM-MS/MS could be used to obtain spatial structural information on SOD1 and that the technique could therefore be employed to investigate the conformational changes in mutant SOD1, which is related to amyotrophic lateral sclerosis and other neurodegenerative disorders

    Identification of sequence polymorphisms in the D-Loop region of mitochondrial DNA as a risk factor for gastric cancer

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    <div><p></p><p>The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk in different types of cancers. We investigated the gastric cancer risk profile of D-Loop SNPs in a case-control study. The frequent alleles of nucleotides 73G/A, 235A/G, 309C/C insert, 324C/G, 16,362T/C and 16,519C/T were significantly associated with an increased risk for gastric cancer, whereas the frequent alleles of nucleotides 523–524AC/del were associated with resistance to gastric cancer. In conclusion, SNPs in the mtDNA D-Loop were found to be valuable markers for gastric cancer risk evaluation.</p></div