Relation between penicillin and N -acetylmuramic acid in the binding site of lysozyme

Abstract

It has been known for some time that penicillin exerts its antibiotic action by inhibiting the synthesis of the cell wall mucopeptide polymer in sensitive bacteria. Richmond and I, seeking an explanation for this specificity, suggested that there was a structural similarity between penicillin and N -acetylmuramic acid, one of the components in the polymer, and that penicillin might inhibit one of the enzymes involved in the synthesis of the polymer because of this similarity (Collins & Richmond 1962). It is therefore very interesting to hear that phenoxymethyl-penicillin has a single binding site in the lysozyme molecule, which is also the binding site for α -benzyl- N -acetylmuramic acid (the site number 5, in Dr Phillips’s notation). With the data from the 6 Å resolution picture of these enzyme complexes obtained by Dr Johnson, it is not possible to determine which groups are involved in interactions between lysozyme and the bound molecules of penicillin and benzy- N -acetylmuramic acid. Examination of the lysozyme model in the region where these molecules are bound shows some groups which may be involved in hydrophobic interactions, but few polar groups. This weakens the possibility that the similarity suggested by Richmond and me underlies the interaction between the molecules in these complexes, since we found the maximum similarity to lie in the disposition of polar groups in penicillin and in N -acetylmuramic acid. Briefly, we drew an analogy between the carboxyl groups, between the ring nitrogen atom in penicillin and the ether oxygen atom in the lactyl side-chain of N -acetylmuramic acid, and between the carbonyl groups in the amide links in the two molecules.