SNAPSHOTS OF A MEMBRANE PROTEIN

Abstract

ANTIBIOTIC DESIGNERS will get a boost from the first structural snapshots of an enzyme involved in forming bacterial cell walls. The coveted structures will assist rational design of molecules that can hit this promising but as-yet-untapped target. Drug designers have long considered penicillin-binding proteins (PBPs) to be important drug targets. PBPs are dual-function enzymes that catalyze formation of a key bacterial cell wall component. One of the enzymes' domains, a transpeptidase (TP), is the target of β-lactam antibiotics such as penicillin. From structural studies of other TP enzymes, that interaction is understood. But many bacteria have developed resistance to this interaction, including methicillin-resistant Staphylococcus aureus , which causes infections in hospitals. What has remained obscure is the way drugs interact with the other component of PBPs, the glycosyltransferase (GT) domain, which researchers would also like to use as a drug target. But structures of GTs of this type have not bee...