ИСТИНА

The problem of antibiotic resistance is becoming more important. One of the strategies leading to this phenomenon is kinase-mediated phosphorylation. An example is the AmiN kinase, a member of a new subfamily of AmiN-like kinases. In a recent work, the first steps in studying of the catalytic mechanism of the AmiN kinase with its substrate, antibiotic amicumacin were performed. The authors modelled the behavior of one type of molecular system - ami-neg-no-1mg. It consisted of deprotonated catalytic amino acid residues, protonated and positively-charged amicumacin, deprotonated AMP-PNP or ATP gamma-phosphate, and one magnesium cation. The authors also made the assumption that the location of ATP in the enzyme binding site corresponds to that for the non-hydrolyzable analog AMP-PNP. The assumption about the presence of one metal cation in the active center was made basing on crystallographic data. In other words, we can see poore electron density in the area of the second-magnesium cation location. Such electron density may testify about low occupancy for magnesium cation (for over 20%), about Li+ location in this place and presence of one water molecule in this area. We are trying to verify the existing data and improve our understanding of the features of the AmiN kinase by implementing a more systematic approach to choosing a hypothesis about the enzyme’s active site structure. We are also trying to perform MD using more accurate parameterization of the molecular system. Besides, as I have said, there are some uncertainties regarding the existing X-ray data and the reasons for the presence of a weak electron density in the area of the second metal cation location. All these factors play a vital role in determining the structure of the pre-reaction state