On the way to new antibiotics
New antibiotics will be more effective
thanks to a breakthrough in the field of cryo-electron microscopy
Vladimir Koryagin, Newspaper.Ru
About the article, which tells about a breakthrough in the field of cryo-electron microscopy and published in the prestigious scientific journal Nature, "Gazeta.Ru" was told by one of its authors – Candidate of Physico-Mathematical Sciences, head of the Laboratory of Protein Biosynthesis of the Department of Molecular and Radiation Biophysics of the St. Petersburg Institute of Nuclear Physics named after B.P. Konstantinov of the Kurchatov Institute, senior researcher of the NIC "Nanobiotechnology" of St. Petersburg State Polytechnic University Andrey Konevega.
– Andrey Leonidovich, what is the importance of the published work?
– The first decade of this century was marked by the determination of the structure of the bacterial ribosome by X-ray crystallography. The significance of these studies was recognized by the international scientific community, and in 2009 the Nobel Prize in Chemistry was awarded to three scientists who made the greatest contribution.
Despite the progress made by crystallographers, the possibilities of the cryoelectron microscopy method are much wider and until recently were limited by technical capabilities, including lower resolution. This work is a "turning point", the first example of obtaining the structure of a functional ribosomal complex with a resolution higher than obtained by crystallographic methods.
– What is the main conclusion of the work? What is its novelty?
– In this work, for the first time, the resolution, that is, the accuracy of determining the spatial structure of the ribosomal complex obtained by cryo–electron microscopy (2.65-2.9 angstrom), exceeds the resolution of the structure previously obtained by X-ray crystallography. For the first time, this spatial structure contains all modified ribosomal RNA bases that were not previously included in the structures due to insufficient accuracy. The paper explains the role of modified bases in fine-tuning ribosome functions and in the mechanism of action of antibiotics.
– How will the conclusions given in the article help biologists?
– Bacterial ribosomes are the most important target of modern antibiotic therapy. More than half of the antibiotics used today inhibit various stages of protein biosynthesis on ribosomes. The problems that doctors are already facing in all countries of the world are associated with the emergence of bacterial strains resistant to the antibiotics used. Therefore, the development of new classes of antibiotics and the modification of existing ones are an urgent problem of modern biology and pharmacy. Knowledge of the structural organization of ribosomes is necessary for the development of new effective antibacterial drugs.
– What methods were used in this case?
– Cryoelectronic microscopy is a modern method, the essence of which is to study the structure of biological objects frozen at a temperature of liquid nitrogen (-196 ° C) using an electron microscope.
In recent years, significant progress has been made in the development of both hardware and in the development of specialized methods of computer processing of the received images. To obtain a high-resolution structure, it is not enough to be able to use modern microscopy techniques, it is equally important to prepare the right sample for the study. The ribosome performs precise decoding of mRNA genetic information at high speed. To study the structure, the decoding process must be stopped at the right moment.
In addition to developing an experimental strategy, my tasks included obtaining a functional ribosomal complex fixed at the time of decoding.
– Where were the surveys conducted?
– The work was carried out in one of the leading research centers in Germany - the Institute of Biophysical Chemistry of the Scientific Research Society. Max Planck in the city of Göttingen, employees of the St. Petersburg Institute of Nuclear Physics named after B.P. Konstantinov in Gatchina and specialists from the University of Göttingen also participated in the work.
Modern science is interdisciplinary and international: scientists of various specialties from different countries often unite to conduct research.
Almost all of this work was carried out at the Institute of Biophysical Chemistry, some drugs were obtained in the Russian laboratory. However, the published work is only a small part of our research projects on the study of molecular mechanisms of protein biosynthesis and the development of new antibiotics. Some of the research is carried out entirely on Russian sites, some in cooperation with our colleagues from foreign research centers. The work carried out in Russian laboratories is funded by the Kurchatov Institute Research Center, as well as by grants from the Russian Foundation for Basic Research (RFBR) and the Russian Science Foundation (RNF).
Portal "Eternal youth" http://vechnayamolodost.ru27.02.2015