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Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution
Abstract
The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli , co-crystallized with an S , R -methylphosphinate and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation of two D-alanine substrates is proposed in which a helix dipole and a hydrogen-bonded triad of tyrosine, serine, and glutamic acid assist binding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-lactate ligase (VanA) present in vancomycin-resistant enterococci. A molecular mechanism for the altered specificity of VanA is suggested.
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Cites
The crisis in antibiotic resistance
Neu, H. C. (1992) · Science · doi:10.1126/science.257.5073.1064 · Cited by 2,834
Cited by
Mechanisms of Action of Antimicrobials: Focus on Fluoroquinolones
Hooper, D. C. (2001) · Clinical Infectious Diseases · doi:10.1086/319370 · Cited by 517
Fold Change in Evolution of Protein Structures
Grishin, N. V. (2001) · Journal of Structural Biology · doi:10.1006/jsbi.2001.4335 · Cited by 444
Recent advances in the formation of the bacterial peptidoglycan monomer unit (1985 to 2000)
Heijenoort, J. V. (2001) · Natural Product Reports · doi:10.1039/a804532a · Cited by 408
Prospects for new antibiotics: a molecule-centered perspective
Walsh, C. T., & Wencewicz, T. A. (2014) · The Journal of Antibiotics · doi:10.1038/ja.2013.49 · Cited by 372
Self-citationStructural Perspective of Peptidoglycan Biosynthesis and Assembly
Lovering, A. L., Safadi, S. S., & Strynadka, N. C. J. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061809-112742 · Cited by 329
Metadata
- Authors
- Fan, C., Moews, P. C., Walsh, C. T., & Knox, J. R.
- Venue
- Science
- Published
- 1994-10-21
- Volume
- 266
- Issue
- 5184
- Pages
- 439-443
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1985107413
- Cited by
- 226
- References
- 1
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- closed
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- Fan, C., Moews, P. C., Walsh, C. T., & Knox, J. R. (1994). Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution. Science. https://doi.org/10.1126/science.7939684
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
