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BioAssay: AID 227555

Affinity for Vancomycin (Exp I)

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 more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 227555
Data Source: ChEMBL (224911)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2014-05-20

Data Table ( Complete ):           View All Data
Tested Compounds:
Description:
Title: Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding.

Abstract: 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.
(PMID: 10579833)
Comment
Putative Target:
ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Binding
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Affinity activity commentAffinity activity commentString
2Affinity standard flagAffinity standard flagInteger
3Affinity qualifierAffinity qualifierString
4Affinity published valueAffinity published valueFloatM-1
5Affinity standard valueAffinity standard valueFloatM-1

Data Table (Concise)
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