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Science 21 October 1994:
Vol. 266. no. 5184, pp. 439 - 443
DOI: 10.1126/science.7939684
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Articles

Science, Vol 266, Issue 5184, 439-443
Copyright © 1994 by American Association for the Advancement of Science

articles

Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution

C Fan, PC Moews, CT Walsh, and Knox JR

Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269-3125.

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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F. Van Bambeke, M. Chauvel, P. E. Reynolds, H. S. Fraimow, and P. Courvalin (1999)
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D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB.
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D-Alanyl-D-Lactate and D-Alanyl-D-Alanine Synthesis by D-Alanyl-D-Alanine Ligase from Vancomycin-resistant Leuconostoc mesenteroides. EFFECTS OF A PHENYLALANINE 261TO TYROSINE MUTATION.
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Glutathionylspermidine Metabolism in Escherichia coli.
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Site-directed Mutagenesis of ATP Binding Residues of Biotin Carboxylase. INSIGHT INTO THE MECHANISM OF CATALYSIS.
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