Antibiotic resistance is a growing problem. The antibiotic Vancomycin binds via hydrogen bonding to D-ala-D-ala which is part of an intermediate in Bacterial Cell wall Biosynthesis. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Ala below (Note that D-Ala is just the enantiomer of the naturally occurring amino acid L-Ala.)

Bacteria have gain resistance to vancomycin, e.g. vancomycin resistant enteroccoci (VRE), by changing D-Ala-D-Ala to D-Ala-D-Lac where D-lac is D-lactate. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Lac below

Please indicate how water might hydrogen bond with D-Ala-D-Ala

Please indicate how water might hydrogen bond with D-Ala-D-Lac

This change in hydrogen bonding pattern is all the bacteria needs to survive. Interestingly changing an oxygen in vancomycin aglycone (compound 5 below) to an NH (compound 6 below) restores activity against VRE, strains with D-Ala-D-Lac, and compound 6 is still active against strains with (D-Ala-D-Ala). Why?

From JACS 2011, 133, 13946 by Boger et al.