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Figure 3
Recognition of the D-Ala-D-Ser ligand. (a) Vancomycin's recognition of D-Ala-D-Ser is virtually the same as its binding of D-Ala-D-Ala. Both ligands are shown superimposed here in ball-and-stick representations; carbon atoms in D-Ala-D-Ser are cyan and in D-Ala-D-Ala are yellow. The vancomycin molecule is shown as a blue–gray surface representation. (b) Clusters of conserved water molecules can be observed after superimposing all ten copies of the antibiotic–ligand complex. Waters in cluster 1 (green) form a hydrogen bond with the C-terminal carboxyl­ate of the ligand; those in cluster 2 (blue) hydrogen bond to the serine hydroxyl of the ligand, and those in cluster 3 (orange) form hydrogen bonds to both the serine hydroxyl and the carbonyl oxygen of the penultimate D-Ala residue. (c) Nine of the ten copies of the D-Ala-D-Ser ligand adopt essentially identical binding modes. The ten copies of the antibiotic–ligand complex were superposed using LSQKAB (Kabsch, 1976BB15); only one copy of the antibiotic is shown for clarity. The nine copies of the ligand that adopt similar poses are shown as yellow sticks; the outlier is shown in magenta. The magenta sphere represents a water molecule found in the binding site next to the outlier ligand; this water occupies the position that is filled by the acetyl oxygen in the other nine copies of the antibiotic–ligand complex, and forms a hydrogen bond with an amide nitro­gen on the antibiotic. (d) Enlarged view of the D-Ser ligands shows halogen bonds (dashed lines) formed between the chlorine atom of residue 6 of the antibiotic (green sphere) and the oxygen atom of the serine hydroxyl group. (e) Close contact between the serine hydroxyl of the ligand and the C5 methyl group of the antibiotic vancosamine sugar. The van der Waals radii for the oxygen and carbon atoms are shown as dot surfaces. (f) The presence of the D-Ser side chain (yellow) forces a rotation of the C6 hydroxyl group of the antibiotic's glucose sugar. The glucose conformation shown in gray represents what is observed in the presence of the serine-containing ligand; cyan shows an alternative conformation that is observed with smaller ligands, but which cannot form in the presence of D-Ser.

IUCrJ
Volume 11| Part 2| March 2024| Pages 133-139
ISSN: 2052-2525
https://doi.org/10.1107/S2052252524000289