Sandbox 127: Difference between revisions
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Peptidoglycan transpeptidases (TP), also known as penicillin-binding proteins (PBP), are essential for bacterial cell wall synthesis and catalyze the cross-linking of peptidoglycan polymers during bacterial cell wall synthesis. Beta-lactam (β-lactam) antibiotics, which include the penicillins, cephalosporins, carbapenems, and the monobactam aztreonam (Figure 1); bind and irreversibly inhibit the active site of TP. The overuse and misuse of β-lactam antibiotics has led to strains of Staphylococcus aureus (S. aureus) that are resistant to almost all currently available β-lactams and are often only susceptible to so-called “last resort antibiotics”, such as vancomycin. | Peptidoglycan transpeptidases (TP), also known as penicillin-binding proteins (PBP), are essential for bacterial cell wall synthesis and catalyze the cross-linking of peptidoglycan polymers during bacterial cell wall synthesis. Beta-lactam (β-lactam) antibiotics, which include the penicillins, cephalosporins, carbapenems, and the monobactam aztreonam (Figure 1); bind and irreversibly inhibit the active site of TP. The overuse and misuse of β-lactam antibiotics has led to strains of Staphylococcus aureus (S. aureus) that are resistant to almost all currently available β-lactams and are often only susceptible to so-called “last resort antibiotics”, such as vancomycin. | ||
== Cell Wall Structure == | == Cell Wall Structure == | ||
The bacterial cell wall is crucial for maintaining the structural integrity of bacteria and protects bacteria from osmotic stress and toxic compounds. The cell wall is composed of peptidoglycan (Figure 2 ) and in Gram positive bacterial species (e.g., S. aureus) is many layers thick, while in Gram negative bacterial species (e.g., Escherichia coli) is only a few layers thick. The difference in the number of peptidoglycan layers accounts for the differential staining of these two groups of organisms. . Peptidoglycan consists of a carbohydrate portion: alternating residues of N-acetylmuranic Acid (NAM) and N-acetylglucosamine (NAG) that polymerize to form long chains, and a protein portion: a pentapeptide chain that terminates with two D-alanine (D-Ala) residues. The pentapeptide chains are covalently bound to each NAM residue Rows of peptidoglycan are cross-linked together with pentaglycine chains to form a "mesh-like" structure. This cross-linking reaction is catalyzed by TPs. | The bacterial cell wall is crucial for maintaining the structural integrity of bacteria and protects bacteria from osmotic stress and toxic compounds. The cell wall is composed of peptidoglycan (Figure 2) and in Gram positive bacterial species (e.g., S. aureus) is many layers thick, while in Gram negative bacterial species (e.g., Escherichia coli) is only a few layers thick. The difference in the number of peptidoglycan layers accounts for the differential staining of these two groups of organisms. . Peptidoglycan consists of a carbohydrate portion: alternating residues of N-acetylmuranic Acid (NAM) and N-acetylglucosamine (NAG) that polymerize to form long chains, and a protein portion: a pentapeptide chain that terminates with two D-alanine (D-Ala) residues. The pentapeptide chains are covalently bound to each NAM residue Rows of peptidoglycan are cross-linked together with pentaglycine chains to form a "mesh-like" structure. This cross-linking reaction is catalyzed by TPs. | ||
[[Image:Cell Wall 7 30 2013.jpg|thumb|alt= Alt text| Figure 1. A.Bacterial Cell Wall B.Peptidoglycan with D-Ala-D-Ala substrate |550px]] | [[Image:Cell Wall 7 30 2013.jpg|thumb|alt= Alt text| Figure 1. A.Bacterial Cell Wall B.Peptidoglycan with D-Ala-D-Ala substrate |550px]] | ||
