Inhibition of lysozyme by positively charged groups in the mucopeptide of the bacterial cell wall

The elegant work that has been presented this afternoon has been concerned with the structure of lysozyme in relation to its action on model substrates of small molecular weight, or its inhibition by equally small molecules. The ‘natural’ substrate is presumably the mucopeptide of bacterial cell wall, which is a large, highly complex and insoluble molecule. A portion of a possible structure of a mucopeptide (Tipper & Strominger 1965) in this case from Staphylococcus aureus , is given in figure 51. Evidently in order to facilitate hydrolysis of the glycosidic links on C-1 of muramic acid (and, in the absence of O-acetyl groups, the enzyme is very good at this) lysozyme molecules must be able to approach closely to the relevant part of the polysaccharide backbone. One of the factors that appears to influence this approach of enzyme and substrate is the presence of positive charges on the mucopeptide. Isolated cell walls of Corynebacterium tritici were completely resistant to lysozyme, but could be made sensitive by the action of formamide at 150 °C for 15 min (Perkins 1965). It was found that this procedure did not remove more than 10% of the non-mucopeptide carbohydrate present, but it did formylate the free amino groups of diaminobutyric acid that occurred in the untreated wall. Acetylation by a mild procedure, followed by treatment with alkali to remove any O-acetyl groups, also caused the walls to become susceptible to dissolution by lysozyme.