Quantum chemical studies on the conformational structure of bacterial peptidoglycans and action of penicillin on cell wall

Abstract

A partial conformational analysis of bacterial peptidoglycans has been carried out using semi-empirical quantum chemical calculation at the AM1 level. It is seen that the presence of the four peptide units attached to one of the pyranose rings considerably affects the minimum energy conformation of the N-acetylglucosamine (NAG)– N-acetyl muramic acid (NAM) units obtained in earlier work. However, in agreement with the result of earlier theoretical studies the AM1 method also disfavours a chitin like structure for the glycan moiety of the peptidoglycan. It is also found that in the minimum energy conformation there is a likelihood of formation of several hydrogen bonds between the sidegroups which might further stabilize the structure. The net atomic charges do not seem to be much affected as the conformation changes. The serine unit in the cell wall transmidase enzyme plays an important role in cross linking the peptide tails of successive NAG–NAM units in order to form the bacterial cell wall. A calculation of the total energy of serine+the peptide tail as a function of their separation yields an estimate of the strength of relevant interaction. It is found that this interaction is almost equal in strength to the interaction between serine and a molecule of penicillin. It is inferred that because of this equality the presence of penicillin negatively affects the formation of cell wall in bacteria.