abstracts - Институт катализа им. Г.К. Борескова

PL-1ENZYME CATALYTICAL SITES: BIOINFORMATICS, STRUCTURE AND MODESOF ACTIONVarfolomeyev S.D.N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, RussiaChemistry Department, Moscow Lomonosov State University, Moscow, RussiaE-mail: sdvarf@enz.chem.msu.ruThe modes of action of enzyme catalytical sites are discussed on the basis of modernmethods of bioinformatics, structural analysis as well as molecular and quantum mechanicsmodeling.The methods of bioinformatics permit researchers to reveal the general properties ofenzymes and of their active sites as well as to deepen our insight into the phenomenon ofbiological catalysis.The major structural paradox of enzymatic catalysis is the fact that the giant quantity ofenzymatic reactions, using actually an infinite quantity of proteins, differing in the primarystructure, is based on the use of a quite limited number of sites in general.Comparison of the primary sequences of a large group of enzymes of various classeshelped reveal some unobvious principles of formation of enzyme catalytic sites. Upon a greatstructural variety of enzymes of given catalytic activities, about 5% positions are strictlyconservative. The amino acids forming the catalytic site are always manifested asconservative with the Shennon entropy diminishing to zero. The catalytic sites are formed byacids and bases. In this case, the aspartic acid most frequently occurs in the active site. Anunexpected fact is that the most important amino acid, most frequenting as conservative, isglycine. The author discusses the role of glycine in formation of three-dimensional structureof the active site. The phenomenon of the structural unity in forming-up the catalytic sites ismanifested in comparison, with hydrolases, of active sites of enzyme other than hydrolases.Activation of molecular reactive centers by enzymes of other classes proceeds by the samenucleophile – electrophile mechanisms as participation of hydrolases, often with the use of thesame three-dimensional structures.The disclosed regularities are illustrated by a great number of examples of reactionsinvolving oxido-reductases, synthetases and isomerases.Some results were obtained using the methods of molecular dynamics and molecularmechanics.Development of ideas about molecular modes of action of enzymes in the “classical”approximation is based on qualitative notions of contemporary chemistry, such as7