Virtuelle (Nano) Welten: PDB Molecule of the Month 29: Penicillin Binding Protein

Penicillin Resistance

Of course, bacteria are quick to fight back. Bacteria reproduce very quickly, with dozens of generations every day, so bacterial evolution is very fast. Bacteria have developed many ways to thwart the action of penicillin. Some change the penicillin-binding proteins in subtle ways, so that they still perform their function but do not bind to the drugs. Some develop more effective ways to shield the sensitive enzymes from the drug or methods to pump drugs quickly away from the cell. But the most common method is to create a special enzyme, a beta-lactamase (also called penicillinase) that seeks out the drug and destroys it.

Many beta-lactamases use the same machinery as used by the penicillin-binding proteins--so similar, in fact, than many researchers believe that the beta-lactamases were actually developed by evolutionary modification of penicillin-binding proteins. The penicillin-binding proteins, like the one shown on the left (PDB entry 3pte), use a serine amino acid in their reaction, colored purple here. The serine forms a covalent bond with a peptidoglycan chain, then releases it as it forms the crosslink with another part of the peptidoglycan network. Penicillin binds to this serine but does not release it, thus permanently blocking the active site. Beta-lactamases, like the one shown on the right (PDB entry 4blm), have a similar serine in their active site pocket. Penicillin also binds to this serine, but is then released in an inactivated form. Other beta-lactamases do the same thing, but use a zinc ion instead of a serine amino acid to inactivate the penicillin.

Penicillin-binding Protein

Penicillin Resistance