A simple geometrical model of the electrostatic environment around the catalytic center of the ribosome

Abstract

AbstractThe central function of the large subunit of the ribosome is to catalyze peptide bond formation. This biochemical reaction is conducted at the peptidyl transferase center (PTC). Experimental evidence shows that the catalytic activity is affected by the electrostatic environment around the peptidyl transferase center. The electrostatic field originates from the particular 3-dimensional space distribution in the phosphate moieties of the 23S (archea and bacteria) or 28S (eukarya) rRNA of the large ribosomal subunit as well as the funnel shape of the cavity at its connection with the ribosome exit tunnel. Here, we set up a minimal geometrical model fitting the available x-ray solved structure of the ribonucleoproteic cavity around the catalytic center of the large subunit of the ribosome. The purpose of this phenomenological model is to estimate quantitatively the electrostatic potential and electric field that are experienced during the peptidyl transfer reaction. At least two reasons motivate the need for developing this quantification. First, we inquire whether the electric field in this particular catalytic environment, made only of nucleic acids, is of the same order of magnitude as the one prevailing in catalytic centers of the proteic enzymes counterparts. Second, the protein synthesis rate is dependent on the nature of the amino acid sequentially incorporated in the nascent chain. The activation energy of the catalytic reaction and its detailed kinetics are expected to be dependent on the mechanical work exerted on the amino acids by the electric field, especially when one of the four charged amino acid residues (R, K, E, D) is newly incorporated in the nascent chain. Physical values of the electric field will provide quantitative knowledge of mechanical work, activation energy and kinetics of the peptide bond formation catalysed by the ribosome.