Simultaneous Recognition of a Carboxylate-Containing Ligand and an Intramolecular Surrogate Ligand in the Crystal Structure of an Asymmetric Vancomycin Dimer

Vancomycin is one of the most important and commonly used
antibiotics in hospitals. Despite numerous
investigations, however, it is not clear how vancomycin recognizes its
site of action in the bacterial cell wall. The
increasing incidence of bacterial resistance to vancomycin makes it
imperative to understand these recognition
determinants so that alternative agents may be developed. Herein
we report the first crystal structure of vancomycin.
The structure resolves a long-standing controversy about
carboxylate recognition by vancomycin, suggests a possible
cooperative mechanism linking ligand binding and dimerization, and
demonstrates the operation of a novel
intramolecular flap which occupies the binding site in the absence of
ligand.