Penicillin-binding proteins
Also known as: PBPs, transpeptidases, DD-transpeptidase
Bacterial enzymes that cross-link the peptidoglycan mesh of the cell wall as bacteria grow. Penicillins, cephalosporins and other beta-lactam antibiotics bind them, the wall weakens and the bacterium bursts; human cells have no cell wall, so the drugs spare them.
- Kind
- enzyme
- Also called
- PBPs, transpeptidases, DD-transpeptidase
- Where it is found
- The cytoplasmic membrane of bacteria, facing the cell wall; absent from human cells.
What it does
The bacterial cell wall is a single giant molecule of peptidoglycan, sugar chains cross-linked by short peptides, that holds the cell together against its own high internal pressure. Penicillin-binding proteins are the transpeptidases that make those cross-links, and beta-lactam antibiotics mimic the natural substrate closely enough to bind the active site permanently. Growing bacteria with unfinished walls then lyse, which is why beta-lactams work best on actively dividing organisms and why they are bactericidal. Resistance arises when bacteria make beta-lactamase enzymes that destroy the drug (countered by clavulanic acid in co-amoxiclav), alter their PBPs so the drug no longer binds (the mechanism of MRSA and penicillin-resistant pneumococci), or, in Gram-negative organisms, restrict entry through their outer membrane. Because the target does not exist in humans, side effects come from allergy and from disruption of the body's own bacterial flora rather than from the mechanism itself.
Role in the body
Synthesis and remodelling of bacterial cell-wall peptidoglycan (transpeptidation).