Conformational energy calculation on the peptide part of murein

Abstract

Conformational energy calculations have been carried out on N-acetyl-L-alanyl-D-gamma-glutamyl-L-lysyl-D-alanyl-D-alanine as a model of the peptide moiety of peptidoglycan. Although many conformations were of comparable energy, particular favoured conformations were selected by assuming conformational similarity between the pentapeptide and the tetrapeptide found during biosynthesis subsequent to the cross-linking of the peptide chains in murein. The common feature of these conformations, which include the global minimum of the pentapeptide, is a ring-shaped backbone. The global minimum is stabilised by a hydrogen bond between the -NH group of L-alanine and the -CO group of the penultimate D-alanine. The distance between the D-lactyl group and the side-chain of the diamino acid is about 1.5 nm. The ring-like structures will accomodate chemical modifications that have been observed in peptidoglycan. The present ring-like structure differs considerably from the models proposed as yet. Energetically beta-pleated sheet conformations and a flat 2.2(7) helical structure are not favoured. Furthermore, an alpha helix cannot occur. The suggested new model exhibits no significant relationship to the solid state conformation of beta-lactam antibiotics.