VANCOMYCIN RESISTANCE - STRUCTURE OF D-ALANINE-D-ALANINE LIGASE AT 2.3-ANGSTROM RESOLUTION

The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli, co-crystallized with an S,R-methylphosphinat e and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation o f two D-alanine substrates is proposed in which a helix dipole and a h ydrogen-bonded triad of tyrosine, serine, and glutamic acid assist bin ding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-la ctate ligase (VanA) present in vancomycin-resistant enterococci. A mol ecular mechanism for the altered specificity of VanA is suggested.