Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution
- 21 October 1994
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 266 (5184), 439-443
- https://doi.org/10.1126/science.7939684
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.Keywords
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