A common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:d-alanine ligase of Escherichia coli

Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1172-6. doi: 10.1073/pnas.92.4.1172.


Examination of x-ray crystallographic structures shows the tertiary structure of D-alanine:D-alanine ligase (EC a bacterial cell wall synthesizing enzyme, is similar to that of glutathione synthetase (EC 6.32.3) despite low sequence homology. Both Escherichia coli enzymes, which convert ATP to ADP during ligation to produce peptide products, are made of three domains, each folded around a 4-to 6-stranded beta-sheet core. Sandwiched between the beta-sheets of the C-terminal and central domains of each enzyme is a nonclassical ATP-binding site that contains a common set of spatially equivalent amino acids. In each enzyme, two loops are proposed to exhibit a required flexibility that allows entry of ATP and substrates, provides protection of the acylphosphate intermediate and tetrahedral adduct from hydrolysis during catalysis, and then permits release of products.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Glutathione Synthase / chemistry
  • Glutathione Synthase / metabolism*
  • Hydrolysis
  • Molecular Sequence Data
  • Peptide Synthases / chemistry
  • Peptide Synthases / metabolism*
  • Protein Conformation
  • Protein Folding*


  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Peptide Synthases
  • Glutathione Synthase
  • D-alanylalanine synthetase