ABSTRACT
The sugar residues of the glycopeptide antibiotic vancomycin contribute to the cooperativity of ligand binding, thereby increasing ligand affinity and enhancing antimicrobial activity. To assess the structural basis for these effects, we determined a 0.98 A X-ray crystal structure of the vancomycin aglycon and compared it to structures of several intact vancomycin:ligand complexes. The crystal structure reveals that the aglycon binds acetate anions and forms back-to-back dimeric complexes in a manner similar to that of intact vancomycin. However, the four independent copies of the aglycon in each asymmetric unit of the crystal exhibit a high degree of conformational heterogeneity. These results suggest that the sugar residues, in addition to enlarging and strengthening the dimer interface, provide steric constraints that limit the vancomycin molecule to a relatively small number of productive conformations.
