peptidoglycan L,D-transpeptidase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 2 a peptidoglycan dimer (tetrapeptide) + 3 H2O = a peptidoglycan tetramer with L,D cross-links (L-Lys-D-Asn-L-Lys) + di-trans,poly-cis-undecaprenyl diphosphate + 4 D-alanine. [MetaCyc:RXN-11349]

Peptidoglycan L,D-transpeptidase activity, also known as penicillin-binding proteins (PBPs), is a crucial molecular function involved in bacterial cell wall synthesis. It catalyzes the formation of peptide cross-links between peptidoglycan strands, which are essential for the structural integrity and rigidity of the bacterial cell wall. This activity involves the cleavage of the terminal D-Ala-D-Ala dipeptide from a pentapeptide stem on one peptidoglycan strand and the subsequent transfer of the pentapeptide to the -amino group of a diaminopimelic acid residue (DAP) on another strand. This transpeptidation reaction results in the formation of a peptide cross-link between the two peptidoglycan strands, strengthening the cell wall. The active site of L,D-transpeptidases typically resides in a highly conserved transpeptidase domain, which features a characteristic catalytic triad consisting of three amino acid residues: a lysine, a tyrosine, and a serine. The lysine residue is responsible for interacting with the terminal D-Ala residue of the pentapeptide stem, while the tyrosine residue stabilizes the transition state during the cleavage reaction. The serine residue acts as a nucleophile, attacking the carbonyl group of the D-Ala-D-Ala dipeptide and forming a covalent intermediate. This covalent intermediate is then attacked by the -amino group of the DAP residue, resulting in the formation of the peptide cross-link and the release of the D-Ala-D-Ala dipeptide. The catalytic mechanism of L,D-transpeptidases is highly sensitive to inhibition by antibiotics, such as penicillin, which bind to the active site and prevent the formation of the covalent intermediate. This mechanism of action explains the effectiveness of penicillin and its derivatives in treating bacterial infections.'
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Proteins (1)

Compounds (1)