Vancomycin: conformational consequences of the sugar substituent.
High-resolution, three-dimensional structures of vancomycin and aglyco-vancomycin in DMSO were determined by nuclear magnetic resonance, metric matrix distance geometry, and molecular dynamics calculations. Conformational flexibility fast on the NMR time scale was examined by ensemble-based calculations which apply the experimentally derived restraints as an ensemble average. Two families of conformations of vancomycin, differing in the positioning of the vancosamine substituent, were observed. In contrast, the aglyco-vancomycin adopts only one conformation in solution. The conformations of vancomycin and the aglyco-vancomycin differ in the alignment of the amide protons which participate in the hydrogen-bonding network with the cell-wall precursor and orientation of the aromatic rings relative to the backbone. Therefore, the high-resolution structural characterization provides insight into a possible role of glycosylation on the activity of this important family of antibiotics.
Grdadolnik
S G
SG
National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.
Pristovsek
P
P
Mierke
D F
DF
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D004121:Dimethyl Sulfoxide; D006595:Hexosamines / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D014640:Vancomycin / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D006595:Hexosamines; C001946:vancosamine; D014640:Vancomycin; D004121:Dimethyl Sulfoxide