ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural basis for the evolution of vancomycin resistance D,D-peptidases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
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- Characterization of VldE (Spr1875), a Pneumococcal Two-State l,d-Endopeptidase with a Four-Zinc Cluster in the Active Site.ACS catalysis · 2024Article
- Taxonomic variation, plastic degradation, and antibiotic resistance traits of plastisphere communities in the maturation pond of a wastewater treatment plant.Applied and environmental microbiology · 2024Article
- Identification of pathways to high-level vancomycin resistance in Clostridioides difficile that incur high fitness costs in key pathogenicity traits.PLoS biology · 2024Article
- Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Benzo[a]pyrene stress impacts adaptive strategies and ecological functions of earthworm intestinal viromes.The ISME journal · 2023Article
- Vancomycin Resistance inMicroorganisms · 2022Review
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Molecular dynamics simulations of the secondary-binding site in disaccharide-modified glycopeptide antibiotics.Scientific reports · 2022Article
- Genomic Insights into the Distribution and Phylogeny of Glycopeptide Resistance Determinants within theAntibiotics (Basel, Switzerland) · 2021Article
- Structural Characterization of EnpA D,L-Endopeptidase fromInternational journal of molecular sciences · 2021Article
- Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes.Microbiome · 2020Article
- Molecular mechanisms of vancomycin resistance.Protein science : a publication of the Protein Society · 2020Review
- Cell Wall Hydrolases in Bacteria: Insight on the Diversity of Cell Wall Amidases, Glycosidases and Peptidases Toward Peptidoglycan.Frontiers in microbiology · 2019Review
- Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases.Nature chemical biology · 2018Article
- Peptidoglycan Compositional Analysis of Enterococcus faecalis Biofilm by Stable Isotope Labeling by Amino Acids in a Bacterial Culture.Biochemistry · 2018Article
- Peptidoglycan O-acetylation increases in response to vancomycin treatment in vancomycin-resistant Enterococcus faecalis.Scientific reports · 2017Article
- Article
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
Vancomycin resistance in Gram-positive bacteria is due to production of cell-wall precursors ending in D-Ala-D-Lac or D-Ala-D-Ser, to which vancomycin exhibits low binding affinities, and to the elimination of the high-affinity precursors ending in D-Ala-D-Ala. Depletion of the susceptible high-affinity precursors is catalyzed by the zinc-dependent D,D-peptidases VanX and VanY acting on dipeptide (D-Ala-D-Ala) or pentapeptide (UDP-MurNac-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala), respectively. Some of the vancomycin resistance operons encode VanXY D,D-carboxypeptidase, which hydrolyzes both di- and pentapeptide. The molecular basis for the diverse specificity of Van D,D-peptidases remains unknown. We present the crystal structures of VanXYC and VanXYG in apo and transition state analog-bound forms and of VanXYC in complex with the D-Ala-D-Ala substrate and D-Ala product. Structural and biochemical analysis identified the molecular determinants of VanXY dual specificity. VanXY residues 110-115 form a mobile cap over the catalytic site, whose flexibility is involved in the switch between di- and pentapeptide hydrolysis. Structure-based alignment of the Van D,D-peptidases showed that VanY enzymes lack this element, which promotes binding of the penta- rather than that of the dipeptide. The structures also highlight the molecular basis for selection of D-Ala-ending precursors over the modified resistance targets. These results illustrate the remarkable adaptability of the D,D-peptidase fold in response to antibiotic pressure via evolution of specific structural elements that confer hydrolytic activity against vancomycin-susceptible peptidoglycan precursors.
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