Molecular Insights into the β-Lactam α-Methyl Modulation of <i>Pseudomonas aeruginosa</i> Penicillin-Binding Protein 3 (PBP3): Loop Dynamics and Hydration Network Modulation

side chain disables active site plasticity and consequently impairs the loop mobility required for the influx of water into the active site. These findings provide mechanistic molecular insights into how α-substituent chemistry modulates active site hydration dynamics in PBP3 and support the importance of α-methyl recognition in dd-peptidases. This work also establishes a structural framework for future studies of PBPs and β-lactam drug design relevant to antimicrobial resistance.