I'm trying to figure this out. I cannot find any publications that go into good detail about the chemistry of PBP inhibition by β-lactam antibiotics.
PBPs cross-link adjacent pentapeptides to form peptidoglycan. My understanding is that, in most bacteria, this pentapeptide has a terminal D-Ala-D-Ala dipeptide. The enzyme removes the terminal D-Ala and forms a D-Ala-Enzyme complex, where the enzyme is linked to the rest of the peptide via ester bond to the D-Ala.
However, when PBPs bind to β-lactams, they also form a β-lactam-ester-enzyme complex. However, this complex is more stable so the β-lactam remains in the active site. Why?
Any good publications are also very welcome.
I would also like to ask, is there any reason the "β-lactamoyl-enzyme" complex can't be hydrolysed?