DOI: 10.1073/pnas.150116497. The molecular basis of vancomycin resistance in clinically relevant <i>Enterococci:</i> Crystal structure of <scp>d</scp> -alanyl- <scp>d</scp> -lactate ligase (VanA)

The molecular basis of vancomycin resistance in clinically relevant Enterococci: Crystal structure of d -alanyl- d -lactate ligase (VanA)

10.1073/pnas.150116497

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

d -alanine- d -lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-Å resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for d -alanyl- d -lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over d -alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of d -alanyl- d -lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.

Bibliography

Roper, D. I., Huyton, T., Vagin, A., & Dodson, G. (2000). The molecular basis of vancomycin resistance in clinically relevant Enterococci: Crystal structure of d -alanyl- d -lactate ligase (VanA). Proceedings of the National Academy of Sciences, 97(16), 8921â8925.

Authors 4

David I. Roper (first)
Trevor Huyton (additional)
Alexei Vagin (additional)
Guy Dodson (additional)

References 27 Referenced 60

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	3 years, 2 months ago (June 7, 2022, 12:47 a.m.)
Indexed	2 months, 3 weeks ago (June 6, 2025, 1:48 a.m.)
Issued	25 years, 1 month ago (July 25, 2000)
Published	25 years, 1 month ago (July 25, 2000)
Published Online	25 years, 1 month ago (July 25, 2000)
Published Print	25 years ago (Aug. 1, 2000)

Funders 0

None

BibTeX

@article{Roper_2000, title={The molecular basis of vancomycin resistance in clinically relevant Enterococci: Crystal structure of <scp>d</scp> -alanyl- <scp>d</scp> -lactate ligase (VanA)}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.150116497}, DOI={10.1073/pnas.150116497}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Roper, David I. and Huyton, Trevor and Vagin, Alexei and Dodson, Guy}, year={2000}, month=jul, pages={8921–8925} }

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    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
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}