4muq › Citations

Structural basis for the evolution of vancomycin resistance D,D-peptidases.

Meziane-Cherif D, Stogios PJ, Evdokimova E, Savchenko A, Courvalin P
Proc Natl Acad Sci U S A 111 5872-7 (2014)
Related entries: 4f78, 4mur, 4mus, 4mut, 4oak

Cited: 22 times
EuropePMC logo PMID: 24711382

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.

Articles - 4muq mentioned but not cited (3)

  1. Structural basis for the evolution of vancomycin resistance D,D-peptidases. Meziane-Cherif D, Stogios PJ, Evdokimova E, Savchenko A, Courvalin P. Proc Natl Acad Sci U S A 111 5872-5877 (2014)
  2. Structure of the LdcB LD-carboxypeptidase reveals the molecular basis of peptidoglycan recognition. Hoyland CN, Aldridge C, Cleverley RM, Duchêne MC, Minasov G, Onopriyenko O, Sidiq K, Stogios PJ, Anderson WF, Daniel RA, Savchenko A, Vollmer W, Lewis RJ. Structure 22 949-960 (2014)
  3. Structural Characterization of EnpA D,L-Endopeptidase from Enterococcus faecalis Prophage Provides Insights into Substrate Specificity of M23 Peptidases. Małecki PH, Mitkowski P, Jagielska E, Trochimiak K, Mesnage S, Sabała I. Int J Mol Sci 22 7136 (2021)


Reviews citing this publication (6)

  1. Cell Wall Hydrolases in Bacteria: Insight on the Diversity of Cell Wall Amidases, Glycosidases and Peptidases Toward Peptidoglycan. Vermassen A, Leroy S, Talon R, Provot C, Popowska M, Desvaux M. Front Microbiol 10 331 (2019)
  2. Molecular mechanisms of vancomycin resistance. Stogios PJ, Savchenko A. Protein Sci 29 654-669 (2020)
  3. Old and New Glycopeptide Antibiotics: Action and Resistance. Binda E, Marinelli F, Marcone GL. Antibiotics (Basel) 3 572-594 (2014)
  4. Carbohydrate recognition and lysis by bacterial peptidoglycan hydrolases. Alcorlo M, Martínez-Caballero S, Molina R, Hermoso JA. Curr Opin Struct Biol 44 87-100 (2017)
  5. Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria. Sionov RV, Steinberg D. Microorganisms 10 1239 (2022)
  6. Vancomycin Resistance in Enterococcus and Staphylococcus aureus. Li G, Walker MJ, De Oliveira DMP. Microorganisms 11 24 (2022)

Articles citing this publication (13)

  1. Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes. Moon K, Jeon JH, Kang I, Park KS, Lee K, Cha CJ, Lee SH, Cho JC. Microbiome 8 75 (2020)
  2. Dual antibacterial activities of a chitosan-modified upconversion photodynamic therapy system against drug-resistant bacteria in deep tissue. Li S, Cui S, Yin D, Zhu Q, Ma Y, Qian Z, Gu Y. Nanoscale 9 3912-3924 (2017)
  3. Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases. Li YX, Zhong Z, Hou P, Zhang WP, Qian PY. Nat Chem Biol 14 381-387 (2018)
  4. Structure of the pneumococcal l,d-carboxypeptidase DacB and pathophysiological effects of disabled cell wall hydrolases DacA and DacB. Abdullah MR, Gutiérrez-Fernández J, Pribyl T, Gisch N, Saleh M, Rohde M, Petruschka L, Burchhardt G, Schwudke D, Hermoso JA, Hammerschmidt S. Mol Microbiol 93 1183-1206 (2014)
  5. Peptidoglycan O-acetylation increases in response to vancomycin treatment in vancomycin-resistant Enterococcus faecalis. Chang JD, Foster EE, Wallace AG, Kim SJ. Sci Rep 7 46500 (2017)
  6. Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases. Meziane-Cherif D, Stogios PJ, Evdokimova E, Egorova O, Savchenko A, Courvalin P. mBio 6 e00806 (2015)
  7. Peptidoglycan Compositional Analysis of Enterococcus faecalis Biofilm by Stable Isotope Labeling by Amino Acids in a Bacterial Culture. Chang JD, Wallace AG, Foster EE, Kim SJ. Biochemistry 57 1274-1283 (2018)
  8. Genomic Insights into the Distribution and Phylogeny of Glycopeptide Resistance Determinants within the Actinobacteria Phylum. Andreo-Vidal A, Binda E, Fedorenko V, Marinelli F, Yushchuk O. Antibiotics (Basel) 10 1533 (2021)
  9. Life in the "old bag" yet: structure of peptidoglycan L,D-carboxypeptidases. Cadby IT, Lovering AL. Structure 22 932-934 (2014)
  10. Molecular dynamics simulations of the secondary-binding site in disaccharide-modified glycopeptide antibiotics. Olademehin OP, Shuford KL, Kim SJ. Sci Rep 12 7087 (2022)
  11. Structural and biochemical analyses of the Streptococcus pneumonia L,D-carboxypeptidase DacB. Zhang J, Yang YH, Jiang YL, Zhou CZ, Chen Y. Acta Crystallogr D Biol Crystallogr 71 283-292 (2015)
  12. Benzo[a]pyrene stress impacts adaptive strategies and ecological functions of earthworm intestinal viromes. Xia R, Sun M, Balcázar JL, Yu P, Hu F, Alvarez PJJ. ISME J 17 1004-1014 (2023)
  13. Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus. Hu J, Han X, Ma X, Chen X, Zhou Z, Peng P, Yu Z, Hou Y, Han P, Pang L, Yang Y, Xu J, Wu W. Eur J Clin Microbiol Infect Dis (2023)


Quick links