Assuntos
Grupo dos Citocromos b/química , Proteínas de Escherichia coli , Proteínas de Bactérias/química , Sítios de Ligação , Grupo dos Citocromos b/genética , Grupo dos Citocromos b/metabolismo , Escherichia coli/química , Ligantes , Mutagênese Sítio-Dirigida , Desnaturação Proteica/efeitos dos fármacos , Engenharia de Proteínas , Análise Espectral Raman , Ureia/farmacologiaRESUMO
Telomere-interactive compounds such as TMPyP4 are expected to inhibit telomerase and thus to be potential anti-cancer drugs. We investigated the interaction of porphyrins bearing peripheral cationic heterocycles with G-quadruplex DNA, which contained human telomeric repeats (GGGTTA)4. One of the porphyrins, pPyTTP, was found to bind to the G-quadruplex DNA and to increase the Tm of the G-quadruplex. The positive sign of induced CD for the complex suggested pPyTTP bound to and stabilized the G-quadruplex DNA possibly by groove binding, distinct from that of TMPyP4.
Assuntos
Antineoplásicos/química , DNA/química , Porfirinas/química , Antineoplásicos/metabolismo , Cátions/química , Dicroísmo Circular , DNA/metabolismo , Quadruplex G , Humanos , Substâncias Macromoleculares , Desnaturação de Ácido Nucleico , Sequências Repetitivas de Ácido Nucleico , Espectrofotometria , Telômero/química , TemperaturaRESUMO
20S proteasomes from higher eukaryotes have immunological functions rather than those from archibacteria or yeast. To clarify the mechanism of the sorting and production of antigen-presenting peptides, it is important and worthwhile to determine the structure of mammalian proteasomes using a third generation synchrotron radiation source. Here we report new crystal forms of 20S proteasomes from bovine liver and preliminary structure analysis of them. The crystals belong to the same space group but have different cell dimensions. One crystal (form I) belongs to space group P2(1)2(1)2(1) with unit cell dimensions of a = 124.8, b =197.4, c =323.8 A, and diffracts to 3.0 A resolution. The other crystal (form II) belongs to the same space group with a =115.1, b =205.6, c =316. 0 A, and diffracts to 4.0 A resolution. The diffraction data for the form I crystal provided an interpretable electron density map for presenting the structural differences from yeast proteasomes.