How B-lactam drugs work: Difference between revisions
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<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''> | <StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''> | ||
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.<ref>PMID:26243971</ref> 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. | 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.<ref>PMID:26243971</ref> 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. [[Image:DalaDala_vs_penicillin.png|left|300 px]] | ||
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 <scene name='81/814024/Secondary_structure/1'>secondary structure </scene> 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 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 <scene name='81/814024/Secondary_structure/1'>secondary structure </scene> 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. | ||
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The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> 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 <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> 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 <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance). | The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> 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 <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> 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 <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance). | ||