Specificity of combination between mucopeptide precursors and vancomycin or ristocetin

Perkins, H. R.

doi:10.1042/bj1110195

Cited by 278 publications

(160 citation statements)

References 28 publications

(10 reference statements)

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“…The mechanism by which ristocetin aggregates platelets is not yet known. Previous studies have shown that ristocetin inhibits the synthesis of peptidoglycans in bacterial cell walls either by steric interference with their polymerization or by forming stable complexes with mucopeptide precursors (25)(26)(27). Whether similar interactions with the platelet surface are involved in ristocetin-induced platelet aggregation remains to be determined.…”

Section: Discussionmentioning

confidence: 97%

Defective Ristocetin-Induced Platelet Aggregation in von Willebrand's Disease and its Correction by Factor VIII

Weiss¹,

Rogers²,

Brand³

1973

J. Clin. Invest.

227

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A B S T RA CT The antibiotic ristocetin, in concentrations of 1.0-1.5 mg/ml, aggregated normal platelets in citrated platelet-rich plasma by a mechanism in which the release reaction played only a minor role. Platelet aggregation by ristocetin in a concentration of 1.2 mg/ ml was absent or markedly decreased in 10 patients with von Willebrand's disease. Lesser degrees of abnormality were obtained with a concentration of 1.5 mg/ml. The magnitude of the defect in ristocetin-induced platelet aggregation correlated well with the degree of abnormality of the bleeding time and the levels of antihemophilic factor (AHF, VIIIAHF) procoagulant activity. In all patients, the defect in ristocetin-induced platelet aggregation was corrected in vitro by normal plasma. Correction was also obtained with a fraction of normal cryoprecipitate that eluted in the void volume with VIIIATF after chromatography on a gel that excludes molecules larger than 5 X 10g. A similar fraction, devoid of VIIIAHF activity, obtained from patients with von Willebrand's disease had no corrective effect, but fractions obtained from patients with hemophilia were just as effective as those obtained from normal subjects. The correction activity of plasma and partially purified factor VIII was inhibited by a rabbit antibody to human factor VIII but not by a human antibody against VIIIAHF procoagulant activity. The studies provide further evidence that patients with von Willebrand's disease are deficient in a plasma factor that is necessary for normal platelet function. The activity of this factor appears to be associated with factor VIII but is unrelated to VIIIAHF procoagulant activity.

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Section: Discussionmentioning

confidence: 97%

Defective Ristocetin-Induced Platelet Aggregation in von Willebrand's Disease and its Correction by Factor VIII

Weiss¹,

Rogers²,

Brand³

1973

J. Clin. Invest.

227

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“…Inhibition of bacterial cell-wall growth by vancomycin is based on noncovalent binding of the antibiotic to cell-wall precursors containing the C-terminal sequence KAA (LDD) [15][16][17]. The solution-phase structures of complexes formed between the vancomycin-group antibiotics and several small bacterial cell-wall mimicking peptides have been elucidated using NMR spectroscopy [3, 18 -20] and X-Ray [6, 21,22].…”

Section: Vancomycin-peptide Noncovalent Complexesmentioning

confidence: 99%

Fluorescence lifetime probe of biomolecular conformations

Shi¹,

Parks²

2010

J. Am. Soc. Mass Spectrom.

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Methods have been developed to measure the fluorescence lifetime versus temperature of trapped biomolecular ions derivatized with a fluorescent dye. Previous measurements for different sequences of polyproline peptides demonstrated that quenching rates are related to conformations and their spatial fluctuations. This paper presents the results of extending these methods to study the conformational dynamics of larger biomolecules. Vancomycin-peptide noncovalent complexes in the 1ϩ charge state were studied as a function of temperature for different W-KAA peptide chiralities (L-LDD, D-LDD, L-DLL). Fluorescence-quenching rates, k q , were found to be stereoselective for these different chiralities with relative magnitudesThe variation in fluorescent quenching resulting from switching the chirality of the single Trp residue was readily detectable. Molecular dynamics analysis of complexes formed by W-KAA (L-LDD) and W-KAA(L-DLL) indicates that increased flexibility in the (L-DLL) complex is correlated with reduced quenching rates. Fluorescence measurements were also performed for the Trp-cage protein comparing quenching rates in the 1ϩ, 2ϩ, and 3ϩ charge states for which k q. Measurements of a sequence including a single-point mutation infer the presence of a salt-bridge structure in the 1ϩ charge state and its absence in both the 2ϩ and 3ϩ states. Molecular dynamics structures of Trp-cage indicate that a salt bridge in the 1ϩ charge state produces more compact conformations leading to larger quenching rates based on the quenching mechanism. In both these experimental studies the fluorescence-quenching rates were consistent with changes in structure induced by either intermolecular or intramolecular interactions. (J Am Soc Mass Spectrom 2010, 21, 707-718) © 2010 American Society for Mass Spectrometry P revious measurements [1] of the lifetime of a fluorescent dye covalently bound to polypeptide ions exhibited a quenching rate that depends both on the separation of the dye to a Trp side chain and on the strength of electrostatic fields in the vicinity of the dye. Quenching rates were found to depend on specific peptide sequences giving rise to different conformations and spatial fluctuations characterized by each conformation. Consequently, lifetime measurements provide an opportunity to extract information sensitive to local molecular arrangements and, perhaps more importantly, changes in that arrangement determined by intramolecular and intermolecular interactions. This paper applies lifetime measurements to study two larger biomolecules: the vancomycin-peptide noncovalent complex and the Trp-cage protein. The structures of these biomolecules have been identified in NMR solution measurements; and each has been studied previously in gas-phase measurements. Results of gas-phase studies of the vancomycin-peptide complex infer that specific changes in the peptide ligand chirality lead to different hydrogen binding networks and thus to different conformations. Gas-phase measurements and calculations of Trp-cage protein i...

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“…1a) is a glycopeptide antibiotic that inhibits the final steps of peptidoglycan biosynthesis by binding to the D-Ala-D-Ala dipeptide termini of peptidoglycan precursors so that they cannot be further processed (1,2). The emergence of vancomycin resistance in the last decade has caused considerable concern because this drug is widely used to treat methicillin-resistant Gram-positive infections and there are few alternatives to it.…”

mentioning

confidence: 99%

Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate

Chen

Walker

Sun

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

137

147

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Bacterial transglycosylases are enzymes that couple the disaccharide subunits of peptidoglycan to form long carbohydrate chains. These enzymes are the target of the pentasaccharide antibiotic moenomycin as well as the proposed target of certain glycopeptides that overcome vancomycin resistance. Because bacterial transglycosylases are difficult enzymes to study, it has not previously been possible to evaluate how moenomycin inhibits them or to determine whether glycopeptide analogues directly target them. We have identified transglycosylase assay conditions that enable kinetic analysis of inhibitors and have examined the inhibition of Escherichia coli penicillin-binding protein 1b (PBP1b) by moenomycin as well as by various glycopeptides. We report that chlorobiphenyl vancomycin analogues that are incapable of binding substrates nevertheless inhibit E. coli PBP1b, which shows that these compounds interact directly with the enzyme. These findings support the hypothesis that chlorobiphenyl vancomycin derivatives overcome vanA resistance by targeting bacterial transglycosylases. We have also found that moenomycin is not competitive with respect to the lipid II substrate of PBP1b, as has long been believed. With the development of suitable methods to evaluate bacterial transglycosylases, it is now possible to probe the mechanism of action of some potentially very important antibiotics.

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Specificity of combination between mucopeptide precursors and vancomycin or ristocetin

Cited by 278 publications

References 28 publications

Defective Ristocetin-Induced Platelet Aggregation in von Willebrand's Disease and its Correction by Factor VIII

Defective Ristocetin-Induced Platelet Aggregation in von Willebrand's Disease and its Correction by Factor VIII

Fluorescence lifetime probe of biomolecular conformations

Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate

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