1c0q
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COMPLEX OF VANCOMYCIN WITH 2-ACETOXY-D-PROPANOIC ACID
OverviewOverview
Bacterial resistance to vancomycin has been attributed to the loss of an, intermolecular hydrogen bond between vancomycin and its peptidoglycan, target when cell wall biosynthesis proceeds via depsipeptide intermediates, rather than the usual polypeptide intermediates. To investigate the, relative importance of this hydrogen bond to vancomycin binding, we have, determined crystal structures at 1.0 A resolution for the vancomycin, complexes with three ligands that mimic peptides and depsipeptides found, in vancomycin-sensitive and vancomycin-resistant bacteria:, N-acetylglycine, D-lactic acid, and 2-acetoxy-D-propanoic acid. These, in, conjunction with structures that have been reported previously, indicate, higher-affinity ligands elicit a structural change in the drug not seen, with these low-affinity ligands. They also enable us to define a minimal, set of drug-ligand interactions necessary to confer higher-affinity, binding on a ligand. Most importantly, these structures point to factors, in addition to the loss of an intermolecular hydrogen bond that must be, invoked to explain the weaker affinity of vancomycin for depsipeptide, ligands. These factors are important considerations for the design of, vancomycin analogues to overcome vancomycin resistance.
About this StructureAbout this Structure
1C0Q is a Protein complex structure of sequences from [1] with CL, VAN and LAC as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding., Loll PJ, Kaplan J, Selinsky BS, Axelsen PH, J Med Chem. 1999 Nov 4;42(22):4714-9. PMID:10579833
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