RESUMO
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins reduce the amount of low-density lipoprotein (LDL) cholesterol, which is known as a well-established risk factor for atherosclerosis. Despite the fact that statins have a common pharmacologic target essential to sterol biosynthesis, their efficacy, safety, and potential non-LDL actions vary significantly for different statins. There is a hypothesis that pharmacological features of statins depend on their location in cell membrane, but to the present day there is a lack of information in literature on interactions of statins with the surface of the cell membrane in liquid media. The results of NMR experiments showed that all studied statins form intermolecular complexes with models of cell membranes (dodecylphosphocholine micelles) in water solution. Locations of pravastatin, simvastatin, fluvastatin and cerivastatin on model membranes were established by NOESY NMR data. Distinctions in their positions can explain differences in pharmacological properties of studied compounds.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/química , Espectroscopia de Ressonância Magnética/métodos , Micelas , Fosforilcolina/análogos & derivados , Óxido de Deutério/química , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Monoinsaturados/metabolismo , Fluvastatina , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Indóis/química , Indóis/metabolismo , Fosforilcolina/química , Fosforilcolina/metabolismo , Pravastatina/química , Pravastatina/metabolismo , Sinvastatina/química , Sinvastatina/metabolismoRESUMO
A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel ß-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric ß-barrels.
Assuntos
Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Ressonância Magnética Nuclear Biomolecular/métodos , Simulação por Computador , Dimerização , Micelas , Conformação ProteicaRESUMO
The aim of this work was to study the mechanisms of interaction between pravastatin and cell membranes using model membranes (sodium dodecyl sulfate micelles) by nuclear magnetic resonance spectroscopy methods. On the basis of the nuclear magnetic resonance experiments, it was established that pravastatin can form intermolecular complexes with sodium dodecyl sulfate micelles by the interaction of its hydrophilic groups with the polar surface of the micelle. Conformational features of pravastatin molecule were also studied.
Assuntos
Espectroscopia de Ressonância Magnética/métodos , Pravastatina/química , Dodecilsulfato de Sódio/química , Micelas , Conformação ProteicaRESUMO
The study of the ability of Lactobacillus plantarum 8P-A3 to synthesize nitric oxide (NO) showed that this strain lacks nitrite reductase. However, analysis by the EPR method revealed the presence of nitric oxide synthase activity in this strain. Like mammalian nitric oxide synthase, lactobacillar NO synthase is involved in the formation of nitric oxide from L-arginine. L. plantarum 8P-A3 does not produce NO in the course of denitrification process. The regulatory role of NO in symbiotic bacteria is discussed.
