Journal of Molecular Evolution

, Volume 42, Issue 6, pp 706–712

Evolution of structure and substrate specificity ind-alanine:d-Alanine ligases and related enzymes

  • Stefan Evers
  • Barbara Casadewall
  • Murielle Charles
  • Sylvie Dutka-Malen
  • Marc Galimand
  • Patrice Courvalin
Articles

Abstract

Thed-alanine:d-alanine-ligase-related enzymes can have three preferential substrate specificities. Usually, these enzymes synthesized-alanyl-d-alanine. In vancomycin-resistant Gram-positive bacteria, structurally related enzymes synthesized-alanyl-d-lactate or Dalanyl-d-serine. The sequence of internal fragments of eight structurald-alanine:d-alanine ligase genes from enterococci has been determined. Alignment of the deduced amino acid sequences with those of other related enzymes from Gram-negative and Gram-positive bacteria revealed the presence of four distinct sequence patterns in the putative substrate-binding sites, each correlating with specificity to a particular substrate (d-alanine:d-lactate ligases exhibited two patterns). Phylogenetic analysis showed different clusters. The enterococcal subtree was largely superimposable on that derived from 16S rRNA sequences. In lactic acid bacteria, structural divergence due to differences in substrate specificity was observed. Glycopeptide resistance proteins VanA and VanB, the VanC-type ligases, and Dd1A and DdlB from enteric bacteria andHaemophilus influenzae constituted separate clusters.

Key words

Cell-wall synthesis Peptidoglycan Enterococcus Glycopeptides Antibiotic resistance 

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Copyright information

© Springer-Verlag New York Inc. 1996

Authors and Affiliations

  • Stefan Evers
    • 1
  • Barbara Casadewall
    • 1
  • Murielle Charles
    • 1
  • Sylvie Dutka-Malen
    • 1
  • Marc Galimand
    • 1
  • Patrice Courvalin
    • 1
  1. 1.Unité des Agents Antibactériens, CNRS EP J0058Institut PasteurParisFrance
  2. 2.F. Hoffmann-La Roche Inc.Pharma Division, Pre-clinical ResearchBaselSwitzerland
  3. 3.Rhône-Poulenc RorerCentre de Recherche, Sce Biol. Antibact.Vitry/SeineFrance

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