How B-lactam drugs work
How beta-lactam drugs work
Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.[1] He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics. 
The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The transpeptidase secondary structure consists of an antiparallel beta sheet, with a small alpha helical subdomain on one side and a large alpha helical domain on the other. The surface of the beta sheet creates a groove where the substrate peptides can bind.
The beta lactam antibiotic binds in this groove of the protein. The groove also contains a serine residue that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a covalent bond with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the nitrogen it bonds to in the lactam ring (a normal C-N bond distance is 0.15 nm; this is almost double that distance). This prevents the normal substrate, the D-ala peptide fragments, from binding to the enzyme, preventing the crosslinking of the bacterial cell wall. Because the antibiotic is attached to the enzyme via a covalent bond, it doesn't come off easily, and the enzyme is essentially "dead". [2] How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread. For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [1] and Penicillin-binding protein. See also Beta-lactam antibiotics
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