CYSTEINYL-TRANSFER RNA-SYNTHETASE FROM ESCHERICHIA-COLI DOES NOT NEED AN EDITING MECHANISM TO REJECT SERINE AND ALANINE - HIGH BINDING-ENERGY OF SMALL-GROUPS IN SPECIFIC MOLECULAR-INTERACTIONS

The cysteinyl-tRNA synthetase from Escherichia coli only very slowly activates serine, alanine, and α-aminobutyrate, the possible competitors of cysteine. The upper limits on the values of kcat/KM for the amino acid dependent ATP/pyrophosphate exchange reactions, relative to that of cysteine, are <10-8, 2X10-7, and 3X10-6, respectively. It is calculated from these data and the concentrations of the amino acids in vivo that the error rates for the misincorporation of serine and alanine for cysteine are less than 10-9 and 5X10-8, respectively. There is no need for an error correcting mechanism and no evidence has been found to implicate one: there is no detectable ATP/pyrophosphatase activity of the enzyme in the presence of tRNACys and alanine; Ala-tRNACys has been synthesized by the reductive desulfurization of Cys-tRNACys and has been found to be relatively resistant to the enzyme-catalyzed deacylation. Part of the high selectivity of the enzyme for the -SH group of cysteine (~5 kcal/mol) appears to be caused by dispersion forces: simple calculations suggest that the dispersion energy between sulfur and a methylene group is about 2.5 times greater than that between two methylene groups. This high “hydrophobicity” of sulfur is consistent with the relative binding energies of substrates of the methionyl-tRNA synthetase. The rest of the high binding energy of the -SH group may come from hydrogen bonding. © 1979, American Chemical Society. All rights reserved.