A detailed model of the active centre of Escherichia coli peptidyl transferase

On the basis of published data, a detailed model of the active centre of Escherichia coli peptidyl transferase is proposed. The major conclusions are as follows: A binding site is present at each of the acceptor (A′) and donor (P′) substrate binding sites of the enzyme for the 3′-terminal CpCpA of aminoacyl- and peptidyl-tRNA, respectively. In particular, the acceptor CpCpA binding site is composed of sites for the following groups: the terminal adenine, the first phosphoryl residue from the 3′-terminus, the 3′-penultimate cytosine, and the second 3′-CMP residue. In addition, two binding sites are present on each of the A′ and P′ sites, one for the basic and one for the hydrophobic aminoacyl R groups of both aminoacyl-tRNA and the carboxyl-terminal amino acid of peptidyl-tRNA. The role of these sites in the binding of inhibitors and substrates and in the mechanism of catalysis of peptide bond formation by peptidyl transferase is discussed.