Enzymology
The structures of penicillin-binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into β-lactam resistance
The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the cross-links in peptidoglycan chains that define the bacterial cell wall. These enzymes are the targets of β-lactam antibiotics, as their inhibition reduces the structural integrity of the cell wall. Bacterial resistance to antibiotics is a rapidly growing concern; however, the structural underpinnings of PBP-derived antibiotic resistance are poorly understood.Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis
Background: M. tuberculosis LdtMt5 is an LdtMt2 paralog that cross-links peptidoglycan stem peptides.Results: LdtMt5 is structurally divergent, strains lacking LdtMt5 are more susceptible to chemical and environmental stresses, and LdtMt2 cannot compensate for its loss.Conclusion: LdtMt2 and LdtMt5 serve non-redundant roles in peptidoglycan maintenance.Significance: LdtMt5 is necessary for properly maintaining cell wall integrity and should be pursued as a drug target.
