Penicillin binding proteins

Penicillin binding proteins (PBPs) are a group of proteins that are characterized by their ability to bind to penicillin and other beta-lactam antibiotics. These proteins are essential for the synthesis of the bacterial cell wall, specifically in the process of peptidoglycan cross-linking, which provides structural integrity to the cell wall.

Function

PBPs are involved in the final stages of the synthesis of peptidoglycan, a critical component of the bacterial cell wall. They catalyze the cross-linking of the peptidoglycan chains, which is crucial for maintaining the cell wall's strength and rigidity. The inhibition of PBPs by beta-lactam antibiotics, such as penicillin, disrupts this process, leading to weakened cell walls and ultimately, bacterial cell death.

Classification

PBPs are classified into two main groups based on their molecular weight:

• High-molecular-weight PBPs (HMW PBPs)
• Low-molecular-weight PBPs (LMW PBPs)

HMW PBPs are further divided into two classes:

• Class A PBPs, which have both transglycosylase and transpeptidase activities.
• Class B PBPs, which primarily have transpeptidase activity.

Mechanism of Action

PBPs function by binding to the D-Ala-D-Ala terminus of the peptidoglycan precursors. This binding facilitates the cross-linking of the peptidoglycan strands, which is essential for the structural integrity of the bacterial cell wall. Beta-lactam antibiotics mimic the D-Ala-D-Ala structure, allowing them to bind to the active site of PBPs, thereby inhibiting their activity and preventing cell wall synthesis.

Clinical Significance

The inhibition of PBPs by beta-lactam antibiotics is a key mechanism by which these drugs exert their antibacterial effects. However, the emergence of antibiotic resistance has become a significant clinical challenge. Bacteria can develop resistance to beta-lactam antibiotics through various mechanisms, including the production of beta-lactamase enzymes that degrade the antibiotic, and the alteration of PBPs to reduce their affinity for the antibiotic.

Related Proteins

• Beta-lactamase
• Transpeptidase
• Transglycosylase

See Also

• Antibiotic resistance
• Bacterial cell wall
• Peptidoglycan
• Beta-lactam antibiotics